Liposome-mediated gene delivery: A comprehensive review of biophysical parameters, lipid composition and targeting strategies
Review paper
DOI:
https://doi.org/10.5599/admet.3065Keywords:
Cationic lipids, non-viral vector, gene therapy, active targeting, transfectionAbstract
Background and purpose: Gene therapy has emerged as a transformative strategy for treating genetic and acquired disorders, but its clinical success relies heavily on the development of safe, efficient, and target-specific delivery vectors. Experimental approach: The paper systematically analysed published evidence on liposome composition, physicochemical behaviour, targeting strategies, and their applications in delivering diverse nucleic acids, with emphasis on the structure-function relationships of lipid components and the impact of biophysical parameters on transfection efficiency. Key results: Current findings demonstrate that the molecular architecture of cationic, neutral, and anionic lipids, particularly variations in head groups, linkers, and hydrophobic tails, strongly dictates liposome stability, cellular uptake, and cargo release. Biophysical attributes such as vesicle size, zeta potential, membrane fluidity, fusion capacity, and PEGylation were identified as major determinants of in vivo fate. Active targeting through ligands, including antibodies, peptides, folate, and aptamers, enhances cell-specific delivery, while combinatorial approaches with physical enhancement techniques such as sonoporation and electroporation further improve nucleic acid transport. Conclusion: By integrating structural, functional, and application-based insights, this review highlights key design principles for optimizing next-generation liposomal vectors, although challenges remain in achieving consistent in vivo performance and clinical translation. The work advances the field by offering a unified framework to guide rational engineering of liposomal platforms for gene therapy.
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References
[1] F. Arabi, V. Mansouri, N. Ahmadbeigi. Gene therapy clinical trials, where do we go? An overview. Biomedicine and Pharmacotherapy 153 (2022) 113324. https://doi.org/10.1016/j.biopha.2022.113324 DOI: https://doi.org/10.1016/j.biopha.2022.113324
[2] H. Maeda, J. Wu, T. Sawa, Y. Matsumura, K. Hori. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. Journal of Controlled Release 65 (2000) 271-284. https://doi.org/10.1016/S0168-3659(99)00248-5 DOI: https://doi.org/10.1016/S0168-3659(99)00248-5
[3] Y. Barenholz. Doxil-the first FDA-approved nano-drug: lessons learned. Journal of Controlled Release 160 (2012) 117-134. https://doi.org/10.1016/j.jconrel.2012.03.020 DOI: https://doi.org/10.1016/j.jconrel.2012.03.020
[4] S.L. Ginn, A.K. Amaya, I.E. Alexander, M. Edelstein, M.R. Abedi. Gene therapy clinical trials worldwide to 2017: An update. Journal of Gene Medicine 20 (2018) 3015. https://doi.org/10.1002/jgm.3015 DOI: https://doi.org/10.1002/jgm.3015
[5] J.H. Felgner, R. Kumar, C.N. Sridhar, C.J. Wheeler, Y.J. Tsai, R. Border. Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations. Journal of Biological Chemistry 269 (1994) 2550-2561. https://doi.org/10.1016/S0021-9258(17)41980-6 DOI: https://doi.org/10.1016/S0021-9258(17)41980-6
[6] S.M. Moghimi, J. Szebeni. Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Progress in Lipid Research 42 (2003) 463-478. https://doi.org/10.1016/S0163-7827(03)00033-X DOI: https://doi.org/10.1016/S0163-7827(03)00033-X
[7] Y. Xu, F.C. Szoka, Jr. Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection. Biochemistry 35 (1996) 5616-5623. https://doi.org/10.1021/BI9602019 DOI: https://doi.org/10.1021/bi9602019
[8] Y. Liu, J. Mei, Q. Zhang, X. Xiao, Z. Zhu. Recent advances in nonviral vectors for gene delivery. Accounts of Chemical Research 45 (2012) 1117-1126. https://doi.org/10.1021/ar200151m DOI: https://doi.org/10.1021/ar200151m
[9] G. Grygorieva, D. Pylypenko, Y. Krasnopolsky. Liposomes: from August Wassermann to vaccines against COVID-19. ADMET and DMPK 11 (2023) 487-497. https://doi.org/10.5599/admet.1926 DOI: https://doi.org/10.5599/admet.1926
[10] P. Liu, G. Chen, J. Zhang. A Review of Liposomes as a Drug Delivery System: Current Status of Approved Products, Regulatory Environments, and Future Perspectives. Molecules 27 (2022) 1372. https://doi.org/10.3390/molecules27041372 DOI: https://doi.org/10.3390/molecules27041372
[11] A. Jesorka, O. Orwar. Liposomes: technologies and analytical applications. Annual Review of Analytical Chemistry 1 (2008) 801-832. https://doi.org/10.1146/annurev.anchem.1.031207.112747 DOI: https://doi.org/10.1146/annurev.anchem.1.031207.112747
[12] W. Mehnert, K. Mäder. Solid lipid nanoparticles: production, characterization and applications. Advanced Drug Delivery Reviews 47 (2001) 165-196. https://doi.org/10.1016/S0169-409X(01)00105-3 DOI: https://doi.org/10.1016/S0169-409X(01)00105-3
[13] T.M. Allen, P.R. Cullis. Liposomal drug delivery systems: from concept to clinical applications. Advanced Drug Delivery Reviews 65 (2013) 36-48. https://doi.org/10.1016/j.addr.2012.09.037 DOI: https://doi.org/10.1016/j.addr.2012.09.037
[14] F. Ashoori, B. Hajipour-Verdom, M. Satari, P. Abdolmaleki. Polyethylenimine-based iron oxide nanoparticles enhance cisplatin toxicity in ovarian cancer cells in the presence of a static magnetic field. Frontiers in Oncology 13 (2023) 1217800. https://doi.org/10.3389/fonc.2023.1217800 DOI: https://doi.org/10.3389/fonc.2023.1217800
[15] M. Satari, B. Hajipoor, S. Hosseinkhani, P. Abdolmaleki. Investigating the effect of 50 Hz alternating magnetic field on nucleic acid delivery by magnetofection method. Modares Journal of Biotechnology 15 (2024) 22721. https://biot.modares.ac.ir/article_22721_en.html
[16] M. Kazemi-Ashtiyani, B. Hajipour-Verdom, M. Satari, P. Abdolmaleki, S. Hosseinkhani, H. Shaki. Estimating the two graph dextran-stearic acid-spermine polymers based on iron oxide nanoparticles as carrier for gene delivery. Biopolymers 113 (2022) 23491. https://doi.org/10.1002/BIP.23491 DOI: https://doi.org/10.1002/bip.23491
[17] V.P. Torchilin. Recent advances with liposomes as pharmaceutical carriers. Nature Reviews Drug Discovery 4 (2005) 145-160. https://doi.org/10.1073/PNAS.84.21.7413 DOI: https://doi.org/10.1038/nrd1632
[18] D.D. Lasic, N.S. Templeton. Liposomes in gene therapy. Advanced Drug Delivery Reviews 20 (1996) 221-266. https://doi.org/10.1038/SJ.GT.3302337 DOI: https://doi.org/10.1016/0169-409X(96)00002-6
[19] P.L. Felgner, T.R. Gadek, M. Holm, R. Roman, H.W. Chan, M. Wenz. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proceedings of the National Academy of Sciences of the United States of America 84 (1987) 7413-7417. https://doi.org/10.1073/PNAS.84.21.7413 DOI: https://doi.org/10.1073/pnas.84.21.7413
[20] D.J. Wells. Gene therapy progress and prospects: electroporation and other physical methods. Gene Therapy 11 (2004) 1363-1369. https://doi.org/10.1038/SJ.GT.3302337 DOI: https://doi.org/10.1038/sj.gt.3302337
[21] H. Yin, R.L. Kanasty, A.A. Eltoukhy, A.J. Vegas, J.R. Dorkin, D.G. Anderson. Non-viral vectors for gene-based therapy. Nature Reviews Genetics 15 (2014) 541-555. https://doi.org/10.1038/NRG3763 DOI: https://doi.org/10.1038/nrg3763
[22] C.M. Newman, T. Bettinger. Gene therapy progress and prospects: ultrasound for gene transfer. Gene Therapy 14 (2007) 465-475. https://doi.org/10.1038/SJ.GT.3302925 DOI: https://doi.org/10.1038/sj.gt.3302925
[23] T. Friedmann, R. Roblin. Gene therapy for human genetic disease? Science 175 (1972) 949-955. https://doi.org/10.1126/science.175.4025.949 DOI: https://doi.org/10.1126/science.175.4025.949
[24] N. Sayed, P. Allawadhi, A. Khurana, V. Singh, U. Navik, S.K. Pasumarthi, I. Khurana, A.K. Banothu, R. Weiskirchen, K.K. Bharani. Gene therapy: Comprehensive overview and therapeutic applications. Life Sciences 294 (2022) 120375. https://doi.org/10.1016/j.lfs.2022.120375 DOI: https://doi.org/10.1016/j.lfs.2022.120375
[25] K.A. High, M.G. Roncarolo. Gene Therapy. New England Journal of Medicine 381 (2019) 455-464. https://doi.org/10.1056/NEJMRA1706910 DOI: https://doi.org/10.1056/NEJMra1706910
[26] A. Fire, S. Xu, M.K. Montgomery, S.A. Kostas, S.E. Driver, C.C. Mello. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391 (1998) 806-811. https://doi.org/10.1038/35888 DOI: https://doi.org/10.1038/35888
[27] C.E. Thomas, A. Ehrhardt, M.A. Kay. Progress and problems with the use of viral vectors for gene therapy. Nature Reviews Genetics 4 (2003) 346-358. https://doi.org/10.1038/NRG1066 DOI: https://doi.org/10.1038/nrg1066
[28] M. Jinek, K. Chylinski, I. Fonfara, M. Hauer, J.A. Doudna, E. Charpentier. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337 (2012) 816-821. https://doi.org/10.1126/science.1225829 DOI: https://doi.org/10.1126/science.1225829
[29] H. Lv, S. Zhang, B. Wang, S. Cui, J. Yan. Toxicity of cationic lipids and cationic polymers in gene deli-very. Journal of Controlled Release 114 (2006) 100-109. https://doi.org/10.1016/j.jconrel.2006.04.014 DOI: https://doi.org/10.1016/j.jconrel.2006.04.014
[30] D.W. Pack, A.S. Hoffman, S. Pun, P.S. Stayton. Design and development of polymers for gene delivery. Nature Reviews Drug Discovery 4 (2005) 581-593. https://doi.org/10.1038/NRD1775 DOI: https://doi.org/10.1038/nrd1775
[31] M.A. Mintzer, E.E. Simanek. Nonviral vectors for gene delivery. Chemical Reviews 109 (2009) 259-302. https://doi.org/10.1021/CR800409E DOI: https://doi.org/10.1021/cr800409e
[32] C.M. Wiethoff, C.R. Middaugh. Barriers to nonviral gene delivery. Journal of Pharmaceutical Sciences 92 (2003) 203-217. https://doi.org/10.1002/jps.10286 DOI: https://doi.org/10.1002/jps.10286
[33] S.D. Conner, S.L. Schmid. Regulated portals of entry into the cell. Nature 422 (2003) 37-44. https://doi.org/10.1038/NATURE01451 DOI: https://doi.org/10.1038/nature01451
[34] G.J. Doherty, H.T. McMahon. Mechanisms of endocytosis. Annual Review of Biochemistry 78 (2009) 857-902. https://doi.org/10.1146/ANNUREV.BIOCHEM.78.081307.110540 DOI: https://doi.org/10.1146/annurev.biochem.78.081307.110540
[35] J. Huotari, A. Helenius. Endosome maturation. The EMBO Journal 30 (2011) 3481-3500. https://doi.org/10.1038/EMBOJ.2011.286 DOI: https://doi.org/10.1038/emboj.2011.286
[36] D.A. Dean, D.D. Strong, W.E. Zimmer. Nuclear entry of nonviral vectors. Gene Therapy 12 (2005) 881-890. https://doi.org/10.1038/SJ.GT.3302534 DOI: https://doi.org/10.1038/sj.gt.3302534
[37] M.L. Read, K.H. Bremner, D. Oupický, N.K. Green, P.F. Searle, L.W. Seymour. Vectors based on reducible polycations facilitate intracellular release of nucleic acids. The Journal of Gene Medicine 5 (2003) 232-241. https://doi.org/10.1002/JGM.331 DOI: https://doi.org/10.1002/jgm.331
[38] S. Simões, V. Slepushkin, N. Düzgünes, M.C. Pedroso de Lima. On the mechanisms of internalization and intracellular delivery mediated by cationic liposomes. Biochimica et Biophysica Acta 1515 (2001) 23-37. https://doi.org/10.1016/S0005-2736(01)00389-3 DOI: https://doi.org/10.1016/S0005-2736(01)00389-3
[39] J.P. Behr, B. Demeneix, J.P. Loeffler, J. Perez-Mutul. Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. Proceedings of the National Academy of Sciences 86 (1989) 6982-6986. https://doi.org/10.1073/PNAS.86.18.6982 DOI: https://doi.org/10.1073/pnas.86.18.6982
[40] E.S. Yang, S. May. Release of cationic polymer-DNA complexes from the endosome: A theoretical investigation of the proton sponge hypothesis. The Journal of Chemical Physics 129 (2008) 185105. https://doi.org/10.1063/1.3009263 DOI: https://doi.org/10.1063/1.3009263
[41] k. Shi, J. Li, Z. Cao, P. Yang, Y. Qiu, B. Yang, Y. Wang, Y. Long, Y. Liu, Q. Zhang, J. Qian, Z. Zhang, H. Gao and Q. He. A pH-responsive cell-penetrating peptide-modified liposomes with active recognizing of integrin αvβ3 for the treatment of melanoma. Control Release 217 (2015) 138-150. https://doi.org/10.1016/j.jconrel.2015.09.009 DOI: https://doi.org/10.1016/j.jconrel.2015.09.009
[42] N. Sayed, P. Allawadhi, A. Khurana, V. Singh, U. Navik, S.K. Pasumarthi, I. Khurana, A.K. Banothu, R. Weiskirchen, K.K. Bharani. Gene therapy: Comprehensive overview and therapeutic applications. Life Sciences 294 (2022) 120375. https://doi.org/10.1016/j.lfs.2022.120375 DOI: https://doi.org/10.1016/j.lfs.2022.120375
[43] M.A. Kay, J.C. Glorioso, L. Naldini. Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nature Medicine 7 (2001) 33-40. https://doi.org/10.1038/83324 DOI: https://doi.org/10.1038/83324
[44] J. Gehl. Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research. Acta Physiologica Scandinavica 177 (2003) 437-447. https://doi.org/10.1046/J.1365-201X.2003.01093.X DOI: https://doi.org/10.1046/j.1365-201X.2003.01093.x
[45] V.P. Torchilin. Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. Annual Review of Biomedical Engineering 8 (2006) 343-375. https://doi.org/10.1016/j.addr.2006.09.009 DOI: https://doi.org/10.1146/annurev.bioeng.8.061505.095735
[46] A.D. Bangham, R.W. Horne. Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. Journal of Molecular Biology 8 (1964) 660-668. https://doi.org/10.1016/S0022-2836(64)80115-7 DOI: https://doi.org/10.1016/S0022-2836(64)80115-7
[47] B. Dizman, M.O. Elasri, L.J. Mathias. Synthesis and antimicrobial activities of new water-soluble bis-quaternary ammonium methacrylate polymers. Journal of Applied Polymer Science 94 (2004) 635-642. https://doi.org/10.1002/app.20872 DOI: https://doi.org/10.1002/app.20872
[48] A. Akbarzadeh, R. Rezaei-Sadabady, S. Davaran, S.W. Joo, N. Zarghami, Y. Hanifehpour. Liposome: classification, preparation, and applications. Nanoscale Research Letters 8 (2013) 102-102. https://doi.org/10.1186/1556-276X-8-102 DOI: https://doi.org/10.1186/1556-276X-8-102
[49] F. Sakurai, T. Nishioka, H. Saito, T. Baba, A. Okuda, O. Matsumoto. Interaction between DNA-cationic liposome complexes and erythrocytes is an important factor in systemic gene transfer via the intravenous route in mice: the role of the neutral helper lipid. Gene Therapy 8 (2001) 677-686. https://doi.org/10.1038/sj.gt.3301460 DOI: https://doi.org/10.1038/sj.gt.3301460
[50] P.K. Maiti, F. Leclercq, M.E. Nabel, M. Antonietti. Gemini surfactants at the air/water interface: a fully atomistic molecular dynamics study. The Journal of Physical Chemistry B 122 (2018) 874-883. https://doi.org/10.1021/jp063343d DOI: https://doi.org/10.1021/jp063343d
[51] A.S. Narang, L. Thoma, D.D. Miller, R.I. Mahato. Cationic lipids with increased DNA binding affinity for nonviral gene transfer in dividing and nondividing cells. Bioconjugate Chemistry 16 (2005) 156-168. https://doi.org/10.1021/bc049818q DOI: https://doi.org/10.1021/bc049818q
[52] H.K. Hall, Jr. Correlation of the base strengths of amines. Journal of the American Chemical Society 79 (1957) 5441-5444. https://doi.org/10.1021/ja01577a030 DOI: https://doi.org/10.1021/ja01577a030
[53] J. Buck, P. Grossen, P.R. Cullis, D. Witzigmann, P. Luciani. Lipid-based DNA therapeutics: hallmarks of non-viral gene delivery. ACS Nano 13 (2019) 3754-3782. https://doi.org/10.1021/acsnano.8b07858 DOI: https://doi.org/10.1021/acsnano.8b07858
[54] D.A. Balazs, W. Godbey. Liposomes for use in gene delivery. Journal of Drug Delivery 2011 (2011) 326497-326497. https://doi.org/10.1155/2011/326497 DOI: https://doi.org/10.1155/2011/326497
[55] M.D. Kearns, K. Patel, J. Dai, J.G. Schellinger, C.C. Appeldoorn, R.N. Zuckermann. 2-Aminoimidazole amino acids as components of the cellular stress response. Biochemistry 47 (2008) 9224-9239. https://doi.org/10.1021/jm100306a DOI: https://doi.org/10.1021/jm100306a
[56] A.J. Lin, N.L. Slack, A. Ahmad, C.X. George, C.E. Samuel, C.R. Safinya. Three-dimensional imaging of lipid gene-carrier: membrane charge density controls universal transfection behavior in lamellar cationic liposome-DNA complexes. Biophysical Journal 84 (2003) 3307-3316. https://doi.org/10.1016/S0006-3495(03)70055-1 DOI: https://doi.org/10.1016/S0006-3495(03)70055-1
[57] H. Farhood, N. Serbina, L. Huang. The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. Biomembranes 1235 (1995) 289-295. https://doi.org/10.1016/0005-2736(95)80016-9 DOI: https://doi.org/10.1016/0005-2736(95)80016-9
[58] X. Gao, L. Huang. A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochemical and Biophysical Research Communications 179 (1991) 280-285. https://doi.org/10.1016/0006-291X(91)91366-K DOI: https://doi.org/10.1016/0006-291X(91)91366-K
[59] R. Leventis, J.R. Silvius. Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biochimica et Biophysica Acta-Biomembranes 1023 (1990) 124-132. https://doi.org/10.1016/0005-2736(90)90017-I DOI: https://doi.org/10.1016/0005-2736(90)90017-I
[60] R. Leventis, J.R. Silvius. Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biomembranes 1023 (1990) 124-132. https://doi.org/10.1016/0005-2736(90)90017-I DOI: https://doi.org/10.1016/0005-2736(90)90017-I
[61] D. Simberg, S. Weisman, Y. Talmon, Y. Barenholz. DOTAP (and other cationic lipids): chemistry, biophysics, and transfection. Critical Reviews in Therapeutic Drug Carrier Systems 21 (2004) 257-317. https://doi.org/10.1615/CRITREVTHERDRUGCARRIERSYST.V21.I4.10 DOI: https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v21.i4.10
[62] J. Ju, M.L. Huan, N. Wan, H. Qiu, S.Y. Zhou, B.L. Zhang. Novel cholesterol-based cationic lipids as transfecting agents of DNA for efficient gene delivery. International Journal of Molecular Sciences 16 (2015) 5666-5681. https://doi.org/10.3390/IJMS16035666 DOI: https://doi.org/10.3390/ijms16035666
[63] S. Huang, H. Que, M. Wang, X. Wei. mRNA vaccines as cancer therapies. Chinese Medical Journal 137 (2024) 2979-2995. https://doi.org/10.1097/CM9.0000000000003455 DOI: https://doi.org/10.1097/CM9.0000000000003455
[64] S. Jain, G. Zon, M. Sundaralingam. Base only binding of spermine in the deep groove of the A-DNA octamer d(GTGTACAC). Biochemistry 28 (1989) 2360-2364. https://doi.org/10.1021/BI00432A002 DOI: https://doi.org/10.1021/bi00432a002
[65] N.J. Zuidam, Y. Barenholz. Electrostatic and structural properties of complexes involving plasmid DNA and cationic lipids commonly used for gene delivery. Biochimica et Biophysica Acta (BBA) - Biomembranes 1368 (1998) 115-128. https://doi.org/10.1016/S0005-2736(97)00187-9 DOI: https://doi.org/10.1016/S0005-2736(97)00187-9
[66] J. Zabner, A.J. Fasbender, T. Moninger, K.A. Poellinger, M.J. Welsh. Cellular and molecular barriers to gene transfer by a cationic lipid. The Journal of Biological Chemistry 270 (1995) 18997-19007. https://doi.org/10.1074/JBC.270.32.18997 DOI: https://doi.org/10.1074/jbc.270.32.18997
[67] P.P. Karmali, A. Chaudhuri. Cationic liposomes as non‐viral carriers of gene medicines: resolved issues, open questions, and future promises. Medicinal Research Reviews 27 (2007) 696-722. https://doi.org/10.1002/med.20090 DOI: https://doi.org/10.1002/med.20090
[68] B.-K. Kim, G.-B. Hwang, Y.-B. Seu, J.-S. Choi, K.S. Jin, K.-O. Doh. DOTAP/DOPE ratio and cell type determine transfection efficiency with DOTAP-liposomes. Biochimica et Biophysica Acta-Biomembranes 1848 (2015) 1996-2001. https://doi.org/10.1016/j.bbamem.2015.06.020 DOI: https://doi.org/10.1016/j.bbamem.2015.06.020
[69] I. Koltover, T. Salditt, J.O. Rädler, C.R. Safinya. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science 281 (1998) 78-81. https://doi.org/10.1126/science.281.5373.78 DOI: https://doi.org/10.1126/science.281.5373.78
[70] S. Chatterjee, E. Kon, P. Sharma, D. Peer. Endosomal escape: A bottleneck for LNP-mediated therapeutics. Proceedings of the National Academy of Sciences 121 (2024) 2307800120. https://doi.org/10.1073/PNAS.2307800120 DOI: https://doi.org/10.1073/pnas.2307800120
[71] T.H. Cheung, M.S. Shoichet. The Interplay of Endosomal Escape and RNA Release from Polymeric Nanoparticles. Langmuir 41 (2025) 7174-7190. https://doi.org/10.1021/acs.langmuir.4c05176 DOI: https://doi.org/10.1021/acs.langmuir.4c05176
[72] I.M. Degors, C. Wang, Z.U. Rehman, I.S. Zuhorn. Carriers break barriers in drug delivery: endocytosis and endosomal escape of gene delivery vectors. Accounts of Chemical Research 52 (2019) 1750-1760. https://doi.org/10.1021/acs.accounts.9b00177 DOI: https://doi.org/10.1021/acs.accounts.9b00177
[73] [70] I.S. Zuhorn, U. Bakowsky, E. Polushkin, W.H. Visser, M.C. Stuart, J.B. Engberts, D. Hoekstra. Nonbilayer phase of lipoplex-membrane mixture determines endosomal escape of genetic cargo and transfection efficiency. Molecular Therapy 11 (2005) 801-810. https://doi.org/10.1016/j.ymthe.2004.12.018 DOI: https://doi.org/10.1016/j.ymthe.2004.12.018
[74] D. Pozzi, C. Marchini, F. Cardarelli, H. Amenitsch, C. Garulli, A. Bifone, G. Caracciolo. Transfection efficiency boost of cholesterol-containing lipoplexes. Biochimica et Biophysica Acta - Biomembranes 1818 (2012) 2335-2343. https://doi.org/10.1016/j.bbamem.2012.05.017 DOI: https://doi.org/10.1016/j.bbamem.2012.05.017
[75] I.S. Zuhorn, R. Kalicharan, D. Hoekstra. Lipoplex-mediated transfection of mammalian cells occurs through the cholesterol-dependent clathrin-mediated pathway of endocytosis. Journal of Biological Chemistry 277 (2002) 18021-18028. https://doi.org/10.1074/jbc.M111257200 DOI: https://doi.org/10.1074/jbc.M111257200
[76] S. Dokka, D. Toledo, X. Shi, V. Castranova, Y. Rojanasakul. Oxygen radical-mediated pulmonary toxicity induced by some cationic liposomes. Pharmaceutical Research 17 (2000) 521-525. https://doi.org/10.1023/A:1007504613351 DOI: https://doi.org/10.1023/A:1007504613351
[77] K. Lappalainen, I. Jääskeläinen, K. Syrjänen, A. Urtti, S. Syrjänen. Comparison of cell proliferation and toxicity assays using two cationic liposomes. Pharmaceutical Research 11 (1994) 1127-1131. https://doi.org/10.1023/a:1018932714745 DOI: https://doi.org/10.1023/A:1018932714745
[78] C. Srinivasan, D.J. Burgess. Optimization and characterization of anionic lipoplexes for gene delivery. Journal of Controlled Release 136 (2009) 62-70. https://doi.org/10.1016/J.JCONREL.2009.01.022 DOI: https://doi.org/10.1016/j.jconrel.2009.01.022
[79] F. Roerdink, N.M. Wassef, E.C. Richardson, C.R. Alving. Effects of negatively charged lipids on phagocytosis of liposomes opsonized by complement. BBA - Biomembranes 734 (1983) 33-39. https://doi.org/10.1016/0005-2736(83)90071-8 DOI: https://doi.org/10.1016/0005-2736(83)90071-8
[80] S.D. Patil, D.G. Rhodes, D.J. Burgess. DNA-based therapeutics and DNA delivery systems: a comprehensive review. The AAPS Journal 7 (2005) 61-77. https://doi.org/10.1208/aapsj070109 DOI: https://doi.org/10.1208/aapsj070109
[81] S. Porte, V. Vadhana, D. Sengupta. A Molecular View of Lipid Nanoparticles: Insights into their Mor¬phology and Structural Plasticity. Small 21 (2025) 05404. https://doi.org/10.1002/SMLL.202505404 DOI: https://doi.org/10.1002/smll.202505404
[82] D. Zhi, S. Zhang, S. Cui, Y. Zhao, Y. Wang, D. Zhao. The headgroup evolution of cationic lipids for gene delivery. Bioconjugate Chemistry 24 (2013) 487-519. https://doi.org/10.1021/BC300381S DOI: https://doi.org/10.1021/bc300381s
[83] R. Koynova, B. Tenchov. Cationic lipids: molecular structure/ transfection activity relationships and interactions with biomembranes. Topics in Current Chemistry 296 (2010) 51-93. https://doi.org/10.1007/128_2010_67 DOI: https://doi.org/10.1007/128_2010_67
[84] S.A. Buckingham, C.J. Garvey, G.G. Warr. Effect of head-group size on micellization and phase behavior in quaternary ammonium surfactant systems. Journal of Physical Chemistry 97 (1993) 10236-10244. https://doi.org/10.1021/J100141A054 DOI: https://doi.org/10.1021/j100141a054
[85] W. Radchatawedchakoon, C. Thongbamrer, W. Konbamrung, P. Khattawee, U. Sakee, W. Roobsoong, J. Sattabongkot, P. Opanasopit, B.E. Yingyongnarongkul. The effect of polar headgroups and spacer length on the DNA transfection of cholesterol-based cationic lipids. RSC Medicinal Chemistry 11 (2020) 212-212. https://doi.org/10.1039/C9MD00459A DOI: https://doi.org/10.1039/C9MD00459A
[86] M. Dittrich, M. Heinze, C. Wölk, S.S. Funari, B. Dobner, H. Möhwald, G. Brezesinski. Structure-function relationships of new lipids designed for DNA transfection. Chemphyschem 12 (2011) 2328-2337. https://doi.org/10.1002/CPHC.201100065 DOI: https://doi.org/10.1002/cphc.201100065
[87] E.F. Palermo, D.K. Lee, A. Ramamoorthy, K. Kuroda. Role of cationic group structure in membrane binding and disruption by amphiphilic copolymers. The Journal of Physical Chemistry B 115 (2011) 366-375. https://doi.org/10.1021/JP1083357 DOI: https://doi.org/10.1021/jp1083357
[88] T.J. Thomas, H.A. Tajmir-Riahi, T. Thomas. Polyamine-DNA interactions and development of gene delivery vehicles. Amino Acids 48 (2016) 2423-2431. https://doi.org/10.1007/S00726-016-2246-8 DOI: https://doi.org/10.1007/s00726-016-2246-8
[89] D. Sun, Z.R. Lu. Structure and Function of Cationic and Ionizable Lipids for Nucleic Acid Delivery. Pharmaceutical Research 40 (2023) 27. https://doi.org/10.1007/S11095-022-03460-2 DOI: https://doi.org/10.1007/s11095-022-03460-2
[90] P.A. Wender, W.C. Galliher, E.A. Goun, L.R. Jones, T.H. Pillow. The design of guanidinium-rich transporters and their internalization mechanisms. Advanced Drug Delivery Reviews 60 (2007) 452. https://doi.org/10.1016/J.ADDR.2007.10.016 DOI: https://doi.org/10.1016/j.addr.2007.10.016
[91] E. Wexselblatt, J.D. Esko, Y. Tor. On guanidinium and cellular uptake. The Journal of Organic Chemistry 79 (2014) 6766-6774. https://doi.org/10.1021/jo501101s DOI: https://doi.org/10.1021/jo501101s
[92] J.B. Rothbard, T.C. Jessop, P.A. Wender. Adaptive translocation: the role of hydrogen bonding and membrane potential in the uptake of guanidinium-rich transporters into cells. Advanced Drug Delivery Reviews 57 (2005) 495-504. https://doi.org/10.1016/j.addr.2004.10.003 DOI: https://doi.org/10.1016/j.addr.2004.10.003
[93] K. Koiwai, K. Tokuhisa, R. Karinaga, Y. Kudo, S. Kusuki, Y. Takeda. Transition from a normal to inverted cylinder for an amidine-bearing lipid/pDNA complex and its excellent transfection. Bioconjugate Chemistry 16 (2005) 1197-1202. https://doi.org/10.1021/bc050164a DOI: https://doi.org/10.1021/bc050164a
[94] M.F. Lensink, C. Lonez, J.-M. Ruysschaert, M. Vandenbranden. Characterization of the cationic diC14-amidine bilayer by mixed DMPC/diC14-amidine molecular dynamics simulations shows an interdigitated nonlamellar bilayer phase. Langmuir 25 (2009) 5230-5238. https://doi.org/10.1021/la804150p DOI: https://doi.org/10.1021/la804150p
[95] M. Frederic, D. Scherman, G. Byk. Introduction of cyclic guanidines into cationic lipids for non-viral gene delivery. Tetrahedron Letters 41 (2000) 675-679. https://doi.org/10.1016/S0040-4039(99)02163-2. DOI: https://doi.org/10.1016/S0040-4039(99)02163-2
[96] J. Herscovici, M.J. Egron, A. Quenot, F. Leclercq, N. Leforestier, N. Mignet, B. Wetzer, D. Scherman. Synthesis of new cationic lipids from an unsaturated glycoside scaffold. Organic letters 3 (2001) 1893-1896. https://doi.org/10.1021/OL0159423. DOI: https://doi.org/10.1021/ol0159423
[97] A. Santel, M. Aleku, O. Keil, J. Endruschat, V. Esche, G. Fisch, S. Dames, K. Löffler, M. Fechtner, W. Arnold, K. Giese, A. Klippel, J. Kaufmann. A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Therapy 13 (2006) 1222-1234. https://doi.org/10.1038/SJ.GT.3302777. DOI: https://doi.org/10.1038/sj.gt.3302777
[98] S. Bhattacharya, A. Bajaj. Advances in gene delivery through molecular design of cationic lipids. Advances in Biochemical Engineering/Biotechnology 117 (2009) 251-283. https://doi.org/10.1039/B900666B DOI: https://doi.org/10.1039/b900666b
[99] I. van der Woude, H.W. Visser, M.B. ter Beest, A. Wagenaar, M.H. Ruiters, J.B. Engberts, D. Hoekstra. Parameters influencing the introduction of plasmid DNA into cells by the use of synthetic amphiphiles as a carrier system. Biochimica et Biophysica Acta-Biomembranes 1240 (1995) 34-40. https://doi.org/10.1016/0005-2736(95)00161-1 DOI: https://doi.org/10.1016/0005-2736(95)00161-1
[100] B. Martin, M. Sainlos, A. Aissaoui, N. Oudrhiri, M. Hauchecorne, J.P. Vigneron, J.M. Lehn, P. Lehn. The Design of Cationic Lipids for Gene Delivery. Current Pharmaceutical Design 11 (2005) 375-394. https://doi.org/10.2174/1381612053382133 DOI: https://doi.org/10.2174/1381612053382133
[101] T. Ren, Y.K. Song, G. Zhang, D. Liu. Structural basis of DOTMA for effective gene delivery. Bioconjugate Chemistry 11 (2000) 452-459. https://doi.org/10.1038/sj.gt.3301153 DOI: https://doi.org/10.1038/sj.gt.3301153
[102] B.K. Kim, K.O. Doh, J.H. Nam, H. Kang, J.G. Park, I.J. Moon, Y.B. Seu. Synthesis of novel cholesterol-based cationic lipids for gene delivery. Bioorganic & Medicinal Chemistry Letters 19 (2009) 2986-2989. https://doi.org/10.1016/J.BMCL.2009.04.036 DOI: https://doi.org/10.1016/j.bmcl.2009.04.036
[103] Y.K. Ghosh, S.S. Visweswariah, S. Bhattacharya. Nature of linkage between the cationic headgroup and cholesteryl skeleton controls gene transfection efficiency. FEBS Letters 473 (2000) 341-344. https://doi.org/10.1016/S0014-5793(00)01558-1 DOI: https://doi.org/10.1016/S0014-5793(00)01558-1
[104] G. Puras, M. Mashal, J. Zárate, M. Agirre, E. Ojeda, S. Grijalvo, R. Eritja, A. Diaz-Tahoces, G. Martínez Navarrete, M. Avilés-Trigueros, E. Fernández, J.L. Pedraz. A novel cationic niosome formulation for gene delivery to the retina. Journal of Controlled Release 174 (2014) 27-36. https://doi.org/10.1016/j.jconrel.2013.11.004 DOI: https://doi.org/10.1016/j.jconrel.2013.11.004
[105] L. Stamatatos, R. Leventis, M.J. Zuckermann, J.R. Silvius. Interactions of cationic lipid vesicles with negatively charged phospholipid vesicles and biological membranes. Biochemistry 27 (1988) 3917-3925. https://doi.org/10.1021/bi00411a005 DOI: https://doi.org/10.1021/bi00411a005
[106] S. Fletcher, A. Ahmad, E. Perouzel, A. Heron, A.D. Miller, M.R. Jorgensen. In vivo studies of dialkynoyl analogues of DOTAP demonstrate improved gene transfer efficiency of cationic liposomes in mouse lung. Journal of Medicinal Chemistry 49 (2006) 349-357. https://doi.org/10.1021/JM0507227 DOI: https://doi.org/10.1021/jm0507227
[107] Q. Liu, W.J. Yi, Y.M. Zhang, J. Zhang, L. Guo, X.Q. Yu. Biotinylated cyclen-contained cationic lipids as non-viral gene delivery vectors. Chemical Biology & Drug Design 82 (2013) 376-383. https://doi.org/10.1111/CBDD.12159 DOI: https://doi.org/10.1111/cbdd.12159
[108] L. Jin, X. Zeng, M. Liu, Y. Deng, N. He. Current progress in gene delivery technology based on chemical methods and nano-carriers. Theranostics 4 (2014) 240-255. https://doi.org/10.7150/THNO.6914 DOI: https://doi.org/10.7150/thno.6914
[109] H.W. Yang, J.W. Yi, E.K. Bang, E.M. Jeon, B.H. Kim. Cationic nucleolipids as efficient siRNA carriers. Organic & Biomolecular Chemistry 9 (2010) 291-296. https://doi.org/10.1039/C0OB00580K DOI: https://doi.org/10.1039/C0OB00580K
[110] J. Voges, R. Reszka, A. Gossmann, C. Dittmar, R. Richter, G. Garlip, L. Kracht, H.H. Coenen, V. Sturm, K. Wienhard, W.D. Heiss, A.H. Jacobs. Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma. Annals of Neurology 54 (2003) 479-487. https://doi.org/10.1002/ANA.10688 DOI: https://doi.org/10.1002/ana.10688
[111] N. Dan. Multilamellar structures of DNA complexes with cationic liposomes. Biophysical Journal 73 (1997) 1842-1846. https://doi.org/10.1016/S0006-3495(97)78214-6 DOI: https://doi.org/10.1016/S0006-3495(97)78214-6
[112] S.R. Paliwal, R. Paliwal, S.P. Vyas. A review of mechanistic insight and application of pH-sensitive lipo¬so¬mes in drug delivery. Drug Delivery 22 (2015) 231-242. https://doi.org/10.3109/10717544.2014.882469 DOI: https://doi.org/10.3109/10717544.2014.882469
[113] T. Boukhnikachvili, O. Aguerre-Chariol, M. Airiau, S. Lesieur, M. Ollivon, J. Vacus. Structure of in-serum transfecting DNA-cationic lipid complexes. FEBS Letters 409 (1997) 188-194. https://doi.org/10.1016/S0014-5793(97)00505-X. DOI: https://doi.org/10.1016/S0014-5793(97)00505-X
[114] S. Zhao, N. Yu, H. Han, S. Guo, N. Murthy. Advances in acid-degradable and enzyme-cleavable linkers for drug delivery. Current Opinion in Chemical Biology 84 (2025) 102552. https://doi.org/10.1016/J.CBPA.2024.102552 DOI: https://doi.org/10.1016/j.cbpa.2024.102552
[115] Y. Zheng, J. Ren, Y. Wu, X. Meng, Y. Zhao, C. Wu. Proteolytic Unlocking of Ultrastable Twin-Acylhydrazone Linkers for Lysosomal Acid-Triggered Release of Anticancer Drugs. Bioconjugate Chemistry 28 (2017) 2620-2626. https://doi.org/10.1021/ACS.BIOCONJCHEM.7B00471 DOI: https://doi.org/10.1021/acs.bioconjchem.7b00471
[116] H. Wen. Redox Sensitive Nanoparticles with Disulfide Bond Linked Sheddable Shell for Intracellular Drug Delivery. Medicinal Chemistry 4 (2014) 748-755. https://doi.org/10.4172/2161-0444.1000225 DOI: https://doi.org/10.4172/2161-0444.1000225
[117] K. Dutta, R. Das, J. Medeiros, S. Thayumanavan. Disulfide Bridging Strategies in Viral and Non-viral Platforms for Nucleic Acid Delivery. Biochemistry 60 (2021) 966-966. https://doi.org/10.1021/ACS.BIOCHEM.0C00860 DOI: https://doi.org/10.1021/acs.biochem.0c00860
[118] H. Hatakeyama, H. Akita, K. Kogure, M. Oishi, Y. Nagasaki, Y. Kihira, M. Ueno, H. Kobayashi, H. Kikuchi, H. Harashima. Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid. Gene Therapy 14 (2007) 68-77. https://doi.org/10.1038/SJ.GT.3302843 DOI: https://doi.org/10.1038/sj.gt.3302843
[119] O. David, V. Diwadkar. Stimuli-responsive gene delivery vectors. Current Opinion in Molecular Therapeutics 5 (2003) 345-350. https://doi.org/14513676
[120] D. Niculescu-Duvaz, J. Heyes, C. Springer. Structure-activity relationship in cationic lipid mediated gene transfection. Current Medicinal Chemistry 10 (2003) 1233-1261. https://doi.org/10.2174/0929867033457476 DOI: https://doi.org/10.2174/0929867033457476
[121] R. Koynova, B. Tenchov. Cationic phospholipids: Structure-transfection activity relationships. Soft Matter 5 (2009) 3187-3200. https://doi.org/10.1039/B902027F DOI: https://doi.org/10.1039/b902027f
[122] C.L. Walsh, J. Nguyen, M.R. Tiffany, F.C. Szoka. Synthesis, Characterization and Evaluation of Ionizable Lysine-Based Lipids for siRNA Delivery. Bioconjugate Chemistry 24 (2012) 36. https://doi.org/10.1021/BC300346H. DOI: https://doi.org/10.1021/bc300346h
[123] C. Pennetta, N. Bono, F. Ponti, M.C. Bellucci, F. Viani, G. Candiani, A. Volonterio. Multifunctional Neomycin-Triazine-Based Cationic Lipids for Gene Delivery with Antibacterial Properties. Bioconjugate Chemistry 32 (2021) 690-701. https://doi.org/10.1021/ACS.BIOCONJCHEM.0C00616 DOI: https://doi.org/10.1021/acs.bioconjchem.0c00616
[124] K.W.C. Mok, P.R. Cullis. Structural and fusogenic properties of cationic liposomes in the presence of plasmid DNA. Biophysical Journal 73 (1997) 2534-2545. https://doi.org/10.1016/S0006-3495(97)78282-1 DOI: https://doi.org/10.1016/S0006-3495(97)78282-1
[125] F. Tang, J.A. Hughes. Synthesis of a single-tailed cationic lipid and investigation of its transfection. Journal of Controlled Release 62 (1999) 345-358. https://doi.org/10.1016/S0168-3659(99)00158-3 DOI: https://doi.org/10.1016/S0168-3659(99)00158-3
[126] L. Wang, R.C. MacDonald. New strategy for transfection: mixtures of medium-chain and long-chain cationic lipids synergistically enhance transfection. Gene Therapy 11 (2004) 1358-1362. https://doi.org/10.1038/SJ.GT.3302297 DOI: https://doi.org/10.1038/sj.gt.3302297
[127] S. Arpicco, S. Canevari, M. Ceruti, E. Galmozzi, F. Rocco, L. Cattel. Synthesis, characterization and transfection activity of new saturated and unsaturated cationic lipids. Farmaco 59 (2004) 869-878. https://doi.org/10.1016/j.farmac.2004.06.007. DOI: https://doi.org/10.1016/j.farmac.2004.06.007
[128] K. Ewert, A. Ahmad, H.M. Evans, H.W. Schmidt, C.R. Safinya. Efficient synthesis and cell-transfection properties of a new multivalent cationic lipid for nonviral gene delivery. Journal of Medicinal Chemistry 45 (2002) 5023-5029. https://doi.org/10.1021/JM020233W DOI: https://doi.org/10.1021/jm020233w
[129] E. Yuba, Y. Nakajima, K. Tsukamoto, S. Iwashita, C. Kojima, A. Harada, K. Kono. Effect of unsaturated alkyl chains on transfection activity of poly(amidoamine) dendron-bearing lipids. Journal of Controlled Release 160 (2012) 552-560. https://doi.org/10.1016/J.JCONREL.2012.04.002 DOI: https://doi.org/10.1016/j.jconrel.2012.04.002
[130] G. Gaynanova, L. Vasileva, R. Kashapov, D. Kuznetsova, R. Kushnazarova, A. Tyryshkina, E. Vasilieva, K. Petrov, L. Zakharova, O. Sinyashin. Self-Assembling Drug Formulations with Tunable Permeability and Biodegradability. Molecules 26 (2021) 6786. https://doi.org/10.3390/MOLECULES26226786 DOI: https://doi.org/10.3390/molecules26226786
[131] A. Bajaj, P. Kondiah, S. Bhattacharya. Effect of the nature of the counteranion on the properties of ani¬onic surfactants. 1. CMC, ionization degree at the CMC and aggregation number of micelles of decyl¬ammonium, dodecylammonium, decyltrimethylammonium, and dodecyltrimethylammonium halides. The Journal of Physical Chemistry B 111 (2007) 1238-1243. https://doi.org/10.1021/j100270a040 DOI: https://doi.org/10.1021/j100270a040
[132] R. Sheng, X. Zhuang, Z. Wang, A. Cao, K. Lin, J.X.X. Zhu. Cationic Nanoparticles Assembled from Natural-Based Steroid Lipid for Improved Intracellular Transport of siRNA and pDNA. Nanomaterial 6 (2016) 69. https://doi.org/10.3390/NANO6040069 DOI: https://doi.org/10.3390/nano6040069
[133] N. Duhem, F. Danhier, V. Préat. Vitamin E-based nanomedicines for anti-cancer drug delivery. Journal of Controlled Release 182 (2014) 33-44. https://doi.org/10.1016/J.JCONREL.2014.03.009 DOI: https://doi.org/10.1016/j.jconrel.2014.03.009
[134] L. Wasungu, D. Hoekstra. Cationic lipids, lipoplexes and intracellular delivery of genes. Journal of Controlled Release 116 (2006) 255-264. https://doi.org/10.1016/j.jconrel.2006.06.024 DOI: https://doi.org/10.1016/j.jconrel.2006.06.024
[135] S. Sun, M. Wang, K.A. Alberti, A. Choy, Q. Xu. DOPE facilitates quaternized lipidoids (QLDs) for in vitro DNA delivery. Nanomedicine: Nanotechnology, Biology and Medicine 9 (2013) 849-854. https://doi.org/10.1016/j.nano.2013.01.006 DOI: https://doi.org/10.1016/j.nano.2013.01.006
[136] H. Chen, H. Zhang, C.M. McCallum, F.C. Szoka, X. Guo. Unsaturated cationic ortho esters for endosome permeation in gene delivery. Journal of Medicinal Chemistry 50 (2007) 4269-4278. https://doi.org/10.1021/jm060128c DOI: https://doi.org/10.1021/jm060128c
[137] D.A. Dean, J.Z. Gasiorowski. Liposome-mediated transfection. Cold Spring Harbor Protocols 2011 (2011) 5583. https://doi.org/10.1101/PDB.PROT5583 DOI: https://doi.org/10.1101/pdb.prot5583
[138] [136] Z. Du, M.M. Munye, A.D. Tagalakis, M.D. Manunta, S.L. Hart. The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations. Scientific Reports 4 (2014) 7107-7107. https://doi.org/10.1038/srep07107 DOI: https://doi.org/10.1038/srep07107
[139] R. Koynova, L. Wang, R.C. MacDonald. Cationic phospholipids forming cubic phases: lipoplex structure and transfection efficiency. Molecular Pharmaceutics 5 (2008) 739-744. https://doi.org/10.1021/MP800011E DOI: https://doi.org/10.1021/mp800011e
[140] A. Nagayasu, K. Uchiyama, H. Kiwada. The size of liposomes: A factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs. Advanced Drug Delivery Reviews 40 (1999) 75-87. https://doi.org/10.1016/S0169-409X(99)00041-1 DOI: https://doi.org/10.1016/S0169-409X(99)00041-1
[141] M.E. Davis, Z. Chen, D.M. Shin. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature Reviews Drug Discovery 7 (2008) 771-782. https://doi.org/10.1038/nrd2614. DOI: https://doi.org/10.1038/nrd2614
[142] M.E. Davis, Z. Chen, D.M. Shin. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature reviews. Drug Discovery 7 (2008) 771-782. https://doi.org/10.1038/NRD2614 DOI: https://doi.org/10.1038/nrd2614
[143] F. Danhier. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? Journal of Controlled Release 244 (2016) 108-121. https://doi.org/10.1016/j.jconrel.2016.11.015 DOI: https://doi.org/10.1016/j.jconrel.2016.11.015
[144] J.W. Nichols, Y.H. Bae. EPR: Evidence and fallacy. Journal of Controlled Release 190 (2014) 451-464. https://doi.org/10.1016/j.jconrel.2014.03.057 DOI: https://doi.org/10.1016/j.jconrel.2014.03.057
[145] G.T. Noble, J.F. Stefanick, J.D. Ashley, T. Kiziltepe, B. Bilgicer. Ligand-targeted liposome design: challenges and fundamental considerations. Trends in Biotechnology 32 (2014) 32-45. https://doi.org/10.1016/J.TIBTECH.2013.09.007 DOI: https://doi.org/10.1016/j.tibtech.2013.09.007
[146] F. Yuan, M. Dellian, D. Fukumura, M. Leunig, D.A. Berk, V.P. Torchilin, R.K. Jain. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Research 55 (1995) 3752-3756. https://doi.org/7641188
[147] S. Chen, J. Zheng, L. Li, S. Jiang. Strong resistance of phosphorylcholine self-assembled monolayers to protein adsorption: insights into nonfouling properties of zwitterionic materials. Journal of the American Chemical Society 127 (2005) 14473-14478. https://doi.org/10.1021/JA054169U DOI: https://doi.org/10.1021/ja054169u
[148] J.B. Schlenoff. Zwitteration: coating surfaces with zwitterionic functionality to reduce nonspecific adsorption. Langmuir 30 (2014) 9625-9636. https://doi.org/10.1021/la500057j DOI: https://doi.org/10.1021/la500057j
[149] N.S. Templeton. Liposomal delivery of nucleic acids in vivo. DNA and Cell Biology 21 (2002) 857-867. https://doi.org/10.1089/104454902762053828 DOI: https://doi.org/10.1089/104454902762053828
[150] A.J. Sodt, M.L. Sandar, K. Gawrisch, R.W. Pastor, E. Lyman. The molecular structure of the liquid-ordered phase of lipid bilayers. Journal of the American Chemical Society 136 (2014) 725-732. https://doi.org/10.1021/ja4105667 DOI: https://doi.org/10.1021/ja4105667
[151] C. Liu, L. Zhang, W. Zhu, R. Guo, H. Sun, X. Chen, N. Deng. Barriers and Strategies of Cationic Liposomes for Cancer Gene Therapy. Molecular Therapy Methods and Clinical Development 18 (2020) 751-764. https://doi.org/10.1016/j.omtm.2020.07.015 DOI: https://doi.org/10.1016/j.omtm.2020.07.015
[152] J.H. Senior, K.R. Trimble, R. Maskiewicz. Interaction of positively-charged liposomes with blood: implications for their application in vivo. BBA - Biomembranes 1070 (1991) 173-179. https://doi.org/10.1016/0005-2736(91)90160-A DOI: https://doi.org/10.1016/0005-2736(91)90160-A
[153] Y. Wang, L. Miao, A. Satterlee, L. Huang. Delivery of oligonucleotides with lipid nanoparticles. Advanced Drug Delivery Reviews 87 (2015) 68-80. https://doi.org/10.1016/j.addr.2015.02.007 DOI: https://doi.org/10.1016/j.addr.2015.02.007
[154] W.H. Abuwatfa, N.S. Awad, W.G. Pitt, G.A. Husseini. Thermosensitive Polymers and Thermo-Responsive Liposomal Drug Delivery Systems. Polymers 14 (2022) 925. https://doi.org/10.3390/polym14050925 DOI: https://doi.org/10.3390/polym14050925
[155] M.Y. Zhuo Dai, X. Yi, Z. Wu, F. Tian, Y. Miao, W. Song, S. He, E. Ahmad, S. Guo, C. Zhu, X. Zhang, Y. Li, X. Shi, R. Wang, Y. Gan. Chain-Length- and Saturation-Tuned Mechanics of Fluid Nanovesicles Direct Tumor Delivery. ACS Nano 13 (2019) 7676-7689. https://doi.org/10.1021/acsnano.9b01181 DOI: https://doi.org/10.1021/acsnano.9b01181
[156] H. Abumanhal-Masarweh, D. da Silva, M. Poley, A. Zinger, E. Goldman, N. Krinsky, R. Kleiner, G. Shenbach, J.E. Schroeder, J. Shklover. Tailoring the lipid composition of nanoparticles modulates their cellular uptake and affects the viability of triple negative breast cancer cells. Journal of Controlled Release 307 (2019) 331–341. https://doi.org/10.1016/j.jconrel.2019.06.025 DOI: https://doi.org/10.1016/j.jconrel.2019.06.025
[157] Y. Liu, K.M. Castro Bravo, J. Liu. Targeted liposomal drug delivery: A nanoscience and biophysical perspective. Nanoscale Horizons 6 (2021) 78-94. https://doi.org/10.1039/D0NH00605J DOI: https://doi.org/10.1039/D0NH00605J
[158] P. Fu, J. Zhang, H. Li, M. Mak, W. Xu, Z. Tao. Extracellular vesicles as delivery systems at nano-/micro-scale. Advanced Drug Delivery Reviews 179 (2021) 113910. https://doi.org/10.1016/j.addr.2021.113910 DOI: https://doi.org/10.1016/j.addr.2021.113910
[159] L.V. Chernomordik, M.M. Kozlov. Mechanics of membrane fusion. Nature Structural and Molecular Biology 15 (2008) 675-683. https://doi.org/10.1038/NSMB.1455;KWRD DOI: https://doi.org/10.1038/nsmb.1455
[160] S. Ohki, Y. Takato. A Molecular Mechanism of Lipid Membrane Fusion. Biophysical Journal 104 (2013) 92. https://doi.org/10.1016/j.bpj.2012.11.550 DOI: https://doi.org/10.1016/j.bpj.2012.11.550
[161] J. Yang, Y. Shimada, R.C. Olsthoorn, B.E. Snaar-Jagalska, H.P. Spaink, A. Kros. Application of coiled coil peptides in liposomal anticancer drug delivery using a zebrafish xenograft model. Acs Nano 10 (2016) 7428–7435. https://doi.org/10.1021/acsnano.6b01410 DOI: https://doi.org/10.1021/acsnano.6b01410
[162] Y. Zeng, M. Shen, A. Singhal, G.J.A. Sevink, N. Crone, A.L. Boyle, A. Kros. Enhanced Liposomal Drug Delivery Via Membrane Fusion Triggered by Dimeric Coiled-Coil Peptides. Small 19 (2023) 2301133. https://doi.org/10.1002/SMLL.202301133 DOI: https://doi.org/10.1002/smll.202301133
[163] A.N. Trementozzi, Z.I. Imam, M. Mendicino, C.C. Hayden, J.C. Stachowiak. Liposome-Mediated Chemotherapeutic Delivery Is Synergistically Enhanced by Ternary Lipid Compositions and Cationic Lipids. Langmuir 35 (2019) 12532-12542. https://doi.org/10.1021/ACS.LANGMUIR.9B01965 DOI: https://doi.org/10.1021/acs.langmuir.9b01965
[164] A.L. Klibanov, K. Maruyama, V.P. Torchilin, L. Huang. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Letters 268 (1990) 235-237. https://doi.org/10.1016/0014-5793(90)81016-H DOI: https://doi.org/10.1016/0014-5793(90)81016-H
[165] K. Abe, K. Higashi, K. Watabe, A. Kobayashi, W. Limwikrant, K. Yamamoto, K. Moribe. Effects of the PEG molecular weight of a PEG-lipid and cholesterol on PEG chain flexibility on liposome surfaces. Colloids and Surfaces A: Physicochemical and Engineering Aspects 474 (2015) 63-70. https://doi.org/10.1016/J.COLSURFA.2015.03.006 DOI: https://doi.org/10.1016/j.colsurfa.2015.03.006
[166] D. Hoekstra, J. Rejman, L. Wasungu, F. Shi, I. Zuhorn. Gene delivery by cationic lipids: in and out of an endosome. Biochemical Society Transactions 35 (2007) 68-71. https://doi.org/10.1042/BST0350068 DOI: https://doi.org/10.1042/BST0350068
[167] A.H. Baker, A. Kritz, L.M. Work, S.A. Nicklin. Cell-selective viral gene delivery vectors for the vasculature. Experimental Physiology 90 (2005) 27-31. https://doi.org/10.1113/EXPPHYSIOL.2004.028126 DOI: https://doi.org/10.1113/expphysiol.2004.028126
[168] Y.Q. Zhang, R.R. Guo, Y.H. Chen, T.C. Li, W.Z. Du, R.W. Xiang, J.B. Guan, Y.P. Li, Y.Y. Huang, Z.Q. Yu, Y. Cai, P. Zhang, G.X. Ling. Ionizable drug delivery systems for efficient and selective gene therapy. Military Medical Research 10 (2023) 1-29. https://doi.org/10.1186/S40779-023-00445-Z DOI: https://doi.org/10.1186/s40779-023-00445-z
[169] A.T. Florence. "Targeting" nanoparticles: the constraints of physical laws and physical barriers. Journal of Controlled Release 164 (2012) 115-124. https://doi.org/10.1016/J.JCONREL.2012.03.022 DOI: https://doi.org/10.1016/j.jconrel.2012.03.022
[170] J.M. Morachis, E.A. Mahmoud, A. Almutairi. Physical and chemical strategies for therapeutic delivery by using polymeric nanoparticles. Pharmacological Reviews 64 (2012) 505-519. https://doi.org/10.1124/pr.111.005363 DOI: https://doi.org/10.1124/pr.111.005363
[171] D.K. Chang, P.C. Li, R.M. Lu, W.N. Jane, H.C. Wu. Peptide-mediated liposomal Doxorubicin enhances drug delivery efficiency and therapeutic efficacy in animal models. PloS One 8 (2013) 83239. https://doi.org/10.1371/JOURNAL.PONE.0083239 DOI: https://doi.org/10.1371/journal.pone.0083239
[172] Z. Jiang, J. Guan, J. Qian, C. Zhan. Peptide ligand-mediated targeted drug delivery of nanomedicines. Biomaterials Science 7 (2019) 461-471. https://doi.org/10.1039/C8BM01340C DOI: https://doi.org/10.1039/C8BM01340C
[173] V. Artemyev, A. Gubaeva, A.I. Paremskaia, A.A. Dzhioeva, A. Deviatkin, S.G. Feoktistova, O. Mityaeva, P.Y. Volchkov. Synthetic Promoters in Gene Therapy: Design Approaches, Features and Applications. Cells 13 (2024) 1963. https://doi.org/10.3390/CELLS13231963 DOI: https://doi.org/10.3390/cells13231963
[174] .M. Nettelbeck, V. Jérôme, R. Müller. Gene therapy: designer promoters for tumour targeting. Trends in Genetics 16 (2000) 174-181. https://doi.org/10.1016/S0168-9525(99)01950-2. DOI: https://doi.org/10.1016/S0168-9525(99)01950-2
[175] W. Alshaer, H. Hillaireau, J. Vergnaud, S. Ismail, E. Fattal. Functionalizing Liposomes with anti-CD44 Aptamer for Selective Targeting of Cancer Cells. Bioconjugate Chemistry 26 (2015) 1307-1313. https://doi.org/10.1021/BC5004313 DOI: https://doi.org/10.1021/bc5004313
[176] J. Gubernator. Active methods of drug loading into liposomes: recent strategies for stable drug entrapment and increased in vivo activity. Expert Opinion on Drug Delivery 8 (2011) 565-580. https://doi.org/10.1517/17425247.2011.566552 DOI: https://doi.org/10.1517/17425247.2011.566552
[177] L.D. Leserman, J.N. Weinstein, R. Blumenthal, W.D. Terry. Receptor-mediated endocytosis of antibody-opsonized liposomes by tumor cells. Proceedings of the National Academy of Sciences 77 (1980) 4089-4093. https://doi.org/10.1073/PNAS.77.7.4089 DOI: https://doi.org/10.1073/pnas.77.7.4089
[178] N. d'Avanzo, G. Torrieri, P. Figueiredo, C. Celia, D. Paolino, A. Correia, K. Moslova, T. Teesalu, M. Fresta, H.A. Santos. LinTT1 peptide-functionalized liposomes for targeted breast cancer therapy. International Journal of Pharmaceutics 597 (2021) 120346-120346. https://doi.org/10.1016/J.IJPHARM.2021.120346 DOI: https://doi.org/10.1016/j.ijpharm.2021.120346
[179] E. Koren, A. Apte, A. Jani, V.P. Torchilin. Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. Journal of Controlled Release 160 (2012) 264-273. https://doi.org/10.1016/J.JCONREL.2011.12.002 DOI: https://doi.org/10.1016/j.jconrel.2011.12.002
[180] D. Paolino, D. Cosco, M. Gaspari, M. Celano, J. Wolfram, P. Voce, E. Puxeddu, S. Filetti, C. Celia, M. Ferrari, D. Russo, M. Fresta. Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nano¬liposomes. Biomaterials 35 (2014) 7101-7109. https://doi.org/10.1016/J.BIOMATERIALS.2014.04.088 DOI: https://doi.org/10.1016/j.biomaterials.2014.04.088
[181] H. Nsairat, D. Khater, U. Sayed, F. Odeh, A. Al Bawab, W. Alshaer. Liposomes: structure, composition, types, and clinical applications. Heliyon 8 (2022) 09394. https://doi.org/10.1016/j.heliyon.2022.e09394 DOI: https://doi.org/10.1016/j.heliyon.2022.e09394
[182] K. Kappler, T. Hennet. Emergence and significance of carbohydrate-specific antibodies. Genes and Immunity 21 (2020) 224-239. https://doi.org/10.1038/S41435-020-0105-9 DOI: https://doi.org/10.1038/s41435-020-0105-9
[183] I. Sela-Culang, V. Kunik, Y. Ofran. The structural basis of antibody-antigen recognition. Frontiers in Immunology 4 (2013) 302. https://doi.org/10.3389/FIMMU.2013.00302 DOI: https://doi.org/10.3389/fimmu.2013.00302
[184] U.J. Björgvinsdóttir, J.B. Larsen, M. Bak, T.L. Andresen, R. Münter. Targeting antibodies dissociate from drug delivery liposomes during blood circulation. Journal of Controlled Release 379 (2025) 982-992. https://doi.org/10.1016/J.JCONREL.2025.01.047 DOI: https://doi.org/10.1016/j.jconrel.2025.01.047
[185] H. Koo, M.S. Huh, I.C. Sun, S.H. Yuk, K. Choi, K. Kim, I.C. Kwon. In vivo targeted delivery of nanopar¬ticles for theranosis. Accounts of Chemical Research 44 (2011) 1018-1028. https://doi.org/10.1021/AR2000138 DOI: https://doi.org/10.1021/ar2000138
[186] M.T. Manzari, Y. Shamay, H. Kiguchi, N. Rosen, M. Scaltriti, D.A. Heller. Targeted drug delivery strategies for precision medicines. Nature Reviews Materials 6 (2021) 351-370. https://doi.org/10.1038/S41578-020-00269-6 DOI: https://doi.org/10.1038/s41578-020-00269-6
[187] F.J. Martin, D. Papahadjopoulos, W.L. Hubbell. Immunospecific targeting of liposomes to cells: a novel and efficient method for covalent attachment of Fab' fragments via disulfide bonds. Biochemistry 20 (1981) 4229-4238. https://doi.org/10.1021/BI00517A043 DOI: https://doi.org/10.1021/bi00517a043
[188] A. Ohradanova-Repic, E. Nogueira, I. Hartl, A.C. Gomes, A. Preto, E. Steinhuber, V. Mühlgrabner, M. Repic, M. Kuttke, A. Zwirzitz, M. Prouza, M. Suchanek, G. Wozniak-Knopp, V. Horejsi, G. Schabbauer, A. Cavaco-Paulo, H. Stockinger. Fab antibody fragment-functionalized liposomes for specific targeting of antigen-positive cells. Nanomedicine: Nanotechnology, Biology And Medicine 14 (2018) 123-130. https://doi.org/10.1016/J.NANO.2017.09.003 DOI: https://doi.org/10.1016/j.nano.2017.09.003
[189] F. Rommasi, N. Esfandiari. Liposomal Nanomedicine: Applications for Drug Delivery in Cancer Therapy. Nanoscale Research Letters 16 (2021) 95. https://doi.org/10.1186/S11671-021-03553-8 DOI: https://doi.org/10.1186/s11671-021-03553-8
[190] A. Adhikari, I.A. Chen. Antibody-Nanoparticle Conjugates in Therapy: Combining the Best of Two Worlds. Small 21 (2025) 2409635. https://doi.org/10.1002/SMLL.202409635 DOI: https://doi.org/10.1002/smll.202409635
[191] S. Gera, E. Kankuri, K. Kogermann. Antimicrobial peptides - Unleashing their therapeutic potential using nanotechnology. Pharmacology & Therapeutics 232 (2022) 107990. https://doi.org/10.1016/J.PHARMTHERA.2021.107990 DOI: https://doi.org/10.1016/j.pharmthera.2021.107990
[192] C. Zylberberg, K. Gaskill, S. Pasley, S. Matosevic. Engineering liposomal nanoparticles for targeted gene therapy. Gene Therapy 24 (2017) 441-452. https://doi.org/10.1038/GT.2017.41 DOI: https://doi.org/10.1038/gt.2017.41
[193] X. Wei, J. Gao, C. Zhan, C. Xie, Z. Chai, D. Ran, M. Ying, P. Zheng, W. Lu. Liposome-based glioma targeted drug delivery enabled by stable peptide ligands. Journal of Controlled Release 218 (2015) 13-21. https://doi.org/10.1016/J.JCONREL.2015.09.059 DOI: https://doi.org/10.1016/j.jconrel.2015.09.059
[194] S. Majumdar, T.J. Siahaan. Peptide-mediated targeted drug delivery. Medicinal Research Reviews 32 (2012) 637-658. https://doi.org/10.1002/MED.20225 DOI: https://doi.org/10.1002/med.20225
[195] Y. Kato, Y. Sugiyama. Targeted delivery of peptides, proteins, and genes by receptor-mediated endocytosis. Critical Reviews in Therapeutic Drug Carrier Systems 14 (1997) 287-331. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v14.i3.30 DOI: https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v14.i3.30
[196] L. Dang, J. Liu, F. Li, L. Wang, D. Li, B. Guo, X. He, F. Jiang, C. Liang, B. Liu, S.A. Badshah, B. He, J. Lu, C. Lu, A. Lu, G. Zhang. Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders. International Journal of Molecular Sciences 17 (2016) 428. https://doi.org/10.3390/IJMS17030428 DOI: https://doi.org/10.3390/ijms17030428
[197] G. Li, Y.Z. Song, Z.J. Huang, K. Chen, D.W. Chen, Y.H. Deng. Novel, nano-sized, liposome-encapsulated polyamidoamine dendrimer derivatives facilitate tumour targeting by overcoming the polyethylene glycol dilemma and integrin saturation obstacle. Journal of Drug Targeting 25 (2017) 734-746. https://doi.org/10.1080/1061186X.2017.1324860 DOI: https://doi.org/10.1080/1061186X.2017.1324860
[198] T. Asai, N. Oku. Liposomalized oligopeptides in cancer therapy. Methods in Enzymology 391 (2005) 163-176. https://doi.org/10.1016/S0076-6879(05)91009-4 DOI: https://doi.org/10.1016/S0076-6879(05)91009-4
[199] O. Al Musaimi, L. Lombardi, D.R. Williams, F. Albericio. Strategies for Improving Peptide Stability and Delivery. Pharmaceuticals 15 (2022) 1283. https://doi.org/10.3390/PH15101283 DOI: https://doi.org/10.3390/ph15101283
[200] Z. Dongrui, M. Miyamoto, H. Yokoo, Y. Demizu. Innovative peptide architectures: advancements in foldamers and stapled peptides for drug discovery. Expert Opinion on Drug Discovery 19 (2024) 699-723. https://doi.org/10.1080/17460441.2024.2350568 DOI: https://doi.org/10.1080/17460441.2024.2350568
[201] Z. Frost, S. Bakhit, C.N. Amaefuna, R.V. Powers, K.V. Ramana. Recent Advances on the Role of B Vitamins in Cancer Prevention and Progression. International Journal of Molecular Sciences 26 (2025) 1967. https://doi.org/10.3390/IJMS26051967 DOI: https://doi.org/10.3390/ijms26051967
[202] H.J. Van de Roovaart, M.M. Stevens, A.E. Goodridge, K.R. Baden, B.G. Sibbitt, E. Delaney, J. Haluschak, S. Kathula, A.M.H. Chen. Safety and efficacy of vitamin B in cancer treatments: A systematic review. Jour¬nal of Oncology Pharmacy Practice 30 (2024) 451-463. https://doi.org/10.1177/10781552231178686 DOI: https://doi.org/10.1177/10781552231178686
[203] W. Weecharangsan, B. Yu, Y. Zheng, S. Liu, J.X. Pang, L.J. Lee, G. Marcucci, R.J. Lee. Efficient delivery of antisense oligodeoxyribonucleotide g3139 by human serum albumin-coated liposomes. Molecular Pharmaceutics 6 (2009) 1848-1855. https://doi.org/10.1021/MP900150G DOI: https://doi.org/10.1021/mp900150g
[204] L. Yang, J. Li, W. Zhou, X. Yuan, S. Li. Targeted delivery of antisense oligodeoxynucleotides to folate receptor-overexpressing tumor cells. Journal of Controlled Release 95 (2004) 321-331. https://doi.org/10.1016/j.jconrel.2003.11.021 DOI: https://doi.org/10.1016/j.jconrel.2003.11.021
[205] Y.G. Assaraf, C.P. Leamon, J.A. Reddy. The folate receptor as a rational therapeutic target for personalized cancer treatment. Drug Resistance Updates 17 (2014) 89-95. https://doi.org/10.1016/J.DRUP.2014.10.002 DOI: https://doi.org/10.1016/j.drup.2014.10.002
[206] J. Sudimack, R.J. Lee. Targeted drug delivery via the folate receptor. Advanced Drug Delivery Reviews 41 (2000) 147-162. https://doi.org/10.1016/S0169-409X(99)00062-9 DOI: https://doi.org/10.1016/S0169-409X(99)00062-9
[207] C.P. Leamon, S.R. Cooper, G.E. Hardee. Folate-liposome-mediated antisense oligodeoxynucleotide targeting to cancer cells: evaluation in vitro and in vivo. Bioconjugate Chemistry 14 (2003) 738-747. https://doi.org/10.1021/BC020089T DOI: https://doi.org/10.1021/bc020089t
[208] X. Chen, X. Wang, Y. Wang, L. Yang, J. Hu, W. Xiao, A. Fu, L. Cai, X. Li, X. Ye, Y. Liu, W. Wu, X. Shao, Y. Mao, Y. Wei, L. Chen. Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide. Journal of Controlled Release 145 (2010) 17-25. https://doi.org/10.1016/j.jconrel.2010.03.007 DOI: https://doi.org/10.1016/j.jconrel.2010.03.007
[209] L. Sercombe, T. Veerati, F. Moheimani, S.Y. Wu, A.K. Sood, S. Hua. Advances and Challenges of Liposome Assisted Drug Delivery. Frontiers in Pharmacology 6 (2015) 00286. https://doi.org/10.3389/FPHAR.2015.00286 DOI: https://doi.org/10.3389/fphar.2015.00286
[210] H.L. Zhang, C. Lv, Z.H. Li, S. Jiang, D. Cai, S.S. Liu, T. Wang, K.H. Zhang. Analysis of aptamer-target binding and molecular mechanisms by thermofluorimetric analysis and molecular dynamics simulation. Frontiers in Chemistry 11 (2023) 1144347. https://doi.org/10.3389/fchem.2023.1144347 DOI: https://doi.org/10.3389/fchem.2023.1144347
[211] Z. Bognár, R.E. Gyurcsányi. Aptamers against Immunoglobulins: Design, Selection and Bioanalytical Applications. International Journal of Molecular Sciences 21 (2020) 1-40. https://doi.org/10.3390/IJMS21165748 DOI: https://doi.org/10.3390/ijms21165748
[212] M. Kim, J.S. Lee, W. Kim, J.H. Lee, B.H. Jun, K.S. Kim, D.E. Kim. Aptamer-conjugated nano-liposome for immunogenic chemotherapy with reversal of immunosuppression. Journal of Controlled Release 348 (2022) 893-910. https://doi.org/10.1016/j.jconrel.2022.06.039 DOI: https://doi.org/10.1016/j.jconrel.2022.06.039
[213] G. Zhou, G. Wilson, L. Hebbard, W. Duan, C. Liddle, J. George, L. Qiao. Aptamers: A promising chemical antibody for cancer therapy. Oncotarget 7 (2016) 13446-13463. https://doi.org/10.18632/ONCOTARGET.7178 DOI: https://doi.org/10.18632/oncotarget.7178
[214] X. Li, Q. Zhao, L. Qiu. Smart ligand: Aptamer-mediated targeted delivery of chemotherapeutic drugs and siRNA for cancer therapy. Journal of Controlled Release 171 (2013) 152-162. https://doi.org/10.1016/j.jconrel.2013.06.006 DOI: https://doi.org/10.1016/j.jconrel.2013.06.006
[215] D. Sanjanwala, V. Patravale. Aptamers and nanobodies as alternatives to antibodies for ligand-targeted drug delivery in cancer. Drug Discovery Today 28 (2023) 103550. https://doi.org/10.1016/J.DRUDIS.2023.103550 DOI: https://doi.org/10.1016/j.drudis.2023.103550
[216] S.E. Baek, K.H. Lee, Y.S. Park, D.K. Oh, S. Oh, K.S. Kim, D.E. Kim. RNA aptamer-conjugated liposome as an efficient anticancer drug delivery vehicle targeting cancer cells in vivo. Journal of Controlled Release 196 (2014) 234-242. https://doi.org/10.1016/J.JCONREL.2014.10.018 DOI: https://doi.org/10.1016/j.jconrel.2014.10.018
[217] D. Rosenblum, A. Gutkin, R. Kedmi, S. Ramishetti, N. Veiga, A.M. Jacobi, M.S. Schubert, D. Friedmann-Morvinski, Z.R. Cohen, M.A. Behlke, J. Lieberman, D. Peer. CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy. Science Advances 6 (2020) 9450. https://doi.org/10.1126/SCIADV.ABC9450 DOI: https://doi.org/10.1126/sciadv.abc9450
[218] W. Ho, M. Gao, F. Li, Z. Li, X.Q. Zhang, X. Xu. Next-Generation Vaccines: Nanoparticle-Mediated DNA and mRNA Delivery. Advanced Healthcare Materials 10 (2021) 2001812. https://doi.org/10.1002/ADHM.202001812 DOI: https://doi.org/10.1002/adhm.202001812
[219] C.M. Lamanna, H. Lusic, M. Camplo, T.J. McIntosh, P. Barthélémy, M.W. Grinstaff. Charge-reversal lipids, peptide-based lipids, and nucleoside-based lipids for gene delivery. Accounts of Chemical Research 45 (2012) 1026-1038. https://doi.org/10.1021/AR200228Y DOI: https://doi.org/10.1021/ar200228y
[220] P. Midoux, C. Pichon, J.J. Yaouanc, P.A. Jaffrès. Chemical vectors for gene delivery: A current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers. British Journal of Pharmacology 157 (2009) 166-178. https://doi.org/10.1111/j.1476-5381.2009.00288.x DOI: https://doi.org/10.1111/j.1476-5381.2009.00288.x
[221] K. Kita, C. Dittrich. Drug delivery vehicles with improved encapsulation efficiency: taking advantage of specific drug-carrier interactions. Expert Opinion on Drug Delivery 8 (2011) 329-342. https://doi.org/10.1517/17425247.2011.553216 DOI: https://doi.org/10.1517/17425247.2011.553216
[222] V. Trivedi, C. Yang, K. Klippel, O. Yegorov, C. von Roemeling, L. Hoang-Minh, G. Fenton, E. Ogando-Rivas, P. Castillo, G. Moore, K. Long-James, K. Dyson, B. Doonan, C. Flores, D.A. Mitchell. mRNA-based precision targeting of neoantigens and tumor-associated antigens in malignant brain tumors. Genome Medicine 16 (2024) 17. https://doi.org/10.1186/S13073-024-01281-Z DOI: https://doi.org/10.1186/s13073-024-01281-z
[223] C. Chakraborty, A.R. Sharma, M. Bhattacharya, S.S. Lee. From COVID-19 to Cancer mRNA Vaccines: Moving From Bench to Clinic in the Vaccine Landscape. Frontiers in Immunology 12 (2021) 679344. https://doi.org/10.3389/FIMMU.2021.679344 DOI: https://doi.org/10.3389/fimmu.2021.679344
[224] M. Ronemus, M.W. Vaughn, R.A. Martienssen. MicroRNA-targeted and small interfering RNA-mediated mRNA degradation is regulated by argonaute, dicer, and RNA-dependent RNA polymerase in Arabidopsis. The Plant Cell 18 (2006) 1559-1574. https://doi.org/10.1105/TPC.106.042127 DOI: https://doi.org/10.1105/tpc.106.042127
[225] L. Aagaard, J.J. Rossi. RNAi therapeutics: Principles, prospects and challenges. Advanced Drug Delivery Reviews 59 (2007) 75-86. https://doi.org/10.1016/j.addr.2007.03.005 DOI: https://doi.org/10.1016/j.addr.2007.03.005
[226] J.K.W. Lam, M.Y.T. Chow, Y. Zhang, S.W.S. Leung. siRNA versus miRNA as therapeutics for gene silencing. Molecular Therapy Nucleic Acids 4 (2015) 252. https://doi.org/10.1038/mtna.2015.23. DOI: https://doi.org/10.1038/mtna.2015.23
[227] H. Isazadeh, F. Oruji, S. Shabani, J. Behroozi, H. Nasiri, A. Isazadeh, M. Akbari. Advances in siRNA delivery approaches in cancer therapy: challenges and opportunities. Molecular Biology Reports 50 (2023) 9529-9543. https://doi.org/10.1007/S11033-023-08749-Y DOI: https://doi.org/10.1007/s11033-023-08749-y
[228] P.R. Cullis, M.J. Hope. Lipid Nanoparticle Systems for Enabling Gene Therapies. Molecular Therapy 25 (2017) 1467-1475. https://doi.org/10.1016/j.ymthe.2017.03.013 DOI: https://doi.org/10.1016/j.ymthe.2017.03.013
[229] J.A. Kulkarni, D. Witzigmann, S. Chen, P.R. Cullis, R. Van Der Meel. Lipid Nanoparticle Technology for Clinical Translation of siRNA Therapeutics. Accounts of Chemical Research 52 (2019) 2435-2444. https://doi.org/10.1021/ACS.ACCOUNTS.9B00368 DOI: https://doi.org/10.1021/acs.accounts.9b00368
[230] L. Han, C. Tang, C. Yin. Oral delivery of shRNA and siRNA via multifunctional polymeric nanoparticles for synergistic cancer therapy. Biomaterials 35 (2014) 4589-4600. https://doi.org/10.1016/J.BIOMATERIALS.2014.02.027 DOI: https://doi.org/10.1016/j.biomaterials.2014.02.027
[231] D. Oliver, H. Ji, P. Liu, A. Gasparian, E. Gardiner, S. Lee, A. Zenteno, L.O. Perinskaya, M. Chen, P. Buckhaults, E. Broude, M.D. Wyatt, H. Valafar, E. Peña, M. Shtutman. Identification of novel cancer therapeutic targets using a designed and pooled shRNA library screen. Scientific Reports 7 (2017) 43023. https://doi.org/10.1038/SREP43023 DOI: https://doi.org/10.1038/srep43023
[232] C.B. Moore, E.H. Guthrie, M.T.H. Huang, D.J. Taxman. Short hairpin RNA (shRNA): design, delivery, and assessment of gene knockdown. Methods in Molecular Biology 629 (2010) 141-158. https://doi.org/10.1007/978-1-60761-657-3_10 DOI: https://doi.org/10.1007/978-1-60761-657-3_10
[233] B.L. Davidson, S.Q. Harper. Viral delivery of recombinant short hairpin RAs. Methods in Enzymology 392 (2005) 145-173. https://doi.org/10.1016/S0076-6879(04)92009-5 DOI: https://doi.org/10.1016/S0076-6879(04)92009-5
[234] C.A. Helliwell, P.M. Waterhouse. Constructs and methods for hairpin RNA-mediated gene silencing in plants. Methods in Enzymology 392 (2005) 24-35. https://doi.org/10.1016/S0076-6879(04)92002-2 DOI: https://doi.org/10.1016/S0076-6879(04)92002-2
[235] S.V. Wesley, Q. Liu, A. Wielopolska, G. Ellacott, N. Smith, S. Singh, C. Helliwell. Custom knock-outs with hairpin RNA-mediated gene silencing. Methods in Molecular Biology 236 (2003) 273-286. https://doi.org/10.1385/1-59259-413-1:273 DOI: https://doi.org/10.1385/1-59259-413-1:273
[236] R.A. Shivdasani. MicroRNAs: regulators of gene expression and cell differentiation. Blood 108 (2006) 3646-3653. https://doi.org/10.1182/BLOOD-2006-01-030015 DOI: https://doi.org/10.1182/blood-2006-01-030015
[237] N. Lynam-Lennon, S.G. Maher, J.V. Reynolds. The roles of microRNA in cancer and apoptosis. Biological Reviews 84 (2009) 55-71. https://doi.org/10.1111/J.1469-185X.2008.00061.X DOI: https://doi.org/10.1111/j.1469-185X.2008.00061.x
[238] G. Yang, B. Yin. The advance of application for microRNAs in cancer gene therapy. Biomedicine & Pharmacotherapy 8 (2014) 137-142. https://doi.org/10.1016/J.BIOPHA.2013.10.002 DOI: https://doi.org/10.1016/j.biopha.2013.10.002
[239] M. Ishida, F.M. Selaru. miRNA-Based Therapeutic Strategies. Current Anesthesiology Reports 1 (2013) 63-70. https://doi.org/10.1007/S40139-012-0004-5 DOI: https://doi.org/10.1007/s40139-012-0004-5
[240] Z. Zhang, Q. Huang, L. Yu, D. Zhu, Y. Li, Z. Xue, Z. Hua, X. Luo, Z. Song, C. Lu, T. Zhao, Y. Liu. The Role of miRNA in Tumor Immune Escape and miRNA-Based Therapeutic Strategies. Frontiers in Immunology 12 (2022) 807895. https://doi.org/10.3389/FIMMU.2021.807895 DOI: https://doi.org/10.3389/fimmu.2021.807895
[241] S. Mehier-Humbert, R.H. Guy. Physical methods for gene transfer: improving the kinetics of gene delivery into cells. Advanced Drug Delivery Reviews 57 (2005) 733-753. https://doi.org/10.1016/J.ADDR.2004.12.007 DOI: https://doi.org/10.1016/j.addr.2004.12.007
[242] M.T. Luiz, J.A.P. Dutra, L.B. Tofani, J.T.C. de Araújo, L.D. Di Filippo, J.M. Marchetti, M. Chorilli. Targeted Liposomes: A Nonviral Gene Delivery System for Cancer Therapy. Pharmaceutics 14 (2022) 821-821. https://doi.org/10.3390/PHARMACEUTICS14040821 DOI: https://doi.org/10.3390/pharmaceutics14040821
[243] S. Song, M.J. Lyle, M.L. Noble-Vranish, D.M. Min-Tran, J. Harrang, W. Xiao, E.C. Unger, C.H. Miao. Ultrasound-mediated gene delivery of factor VIII plasmids for hemophilia A gene therapy in mice. Molecular Therapy Nucleic Acids 27 (2022) 916-926. https://doi.org/10.1016/j.omtn.2022.01.006 DOI: https://doi.org/10.1016/j.omtn.2022.01.006
[244] C.X. Deng, F. Sieling, H. Pan, J. Cui. Ultrasound-induced cell membrane porosity. Ultrasound in Medicine and Biology 30 (2004) 519-526. https://doi.org/10.1016/j.ultrasmedbio.2004.01.005 DOI: https://doi.org/10.1016/j.ultrasmedbio.2004.01.005
[245] H.D. Liang, J. Tang, M. Halliwell. Sonoporation, drug delivery, and gene therapy. Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine 224 (2010) 343-361. https://doi.org/10.1243/09544119JEIM565 DOI: https://doi.org/10.1243/09544119JEIM565
[246] C. Plank, F. Scherer, U. Schillinger, C. Bergemann, M. Anton. Magnetofection: enhancing and targeting gene delivery with superparamagnetic nanoparticles and magnetic fields. Journal of Liposome Research 13 (2003) 29-32. https://doi.org/10.1081/LPR-120017486 DOI: https://doi.org/10.1081/LPR-120017486
[247] F. Javani Jouni, J. Zafari, P. Abdolmaleki, H. Vazini, L. Ghandi, M. Satari. Aflatoxin M1 detoxification from infected milk using Fe3O4 nanoparticles attached to specific aptamer. Journal of Nanostructure in Chemistry 8 (2018) 13-22. https://doi.org/10.1007/S40097-017-0250-5/FIGURES/10 DOI: https://doi.org/10.1007/s40097-017-0250-5
[248] M. Satari, N. Haghighat, F. Javani Jouni, P. Abodolmaleki. The Effects of Synthesized Superpara-mag¬netic Iron Oxide Nanoparticles and Electromagnetic Field on Cell Death of MCF-7 Breast Cancer Cell Line. Multidisciplinary Cancer Investigation 2 (2018) 13-21. https://doi.org/10.30699/ACADPUB.MCI.2.1.13 DOI: https://doi.org/10.30699/acadpub.mci.2.1.13
[249] M. Satari, F.J. Jouni, P. Abolmaleki, H. Soleimani. Influence of Static Magnetic Field on HeLa and Huo2 Cells in the Presence of Aloe vera Extract. Asian Pacific Journal of Cancer Prevention 22 (2021) 9-15. https://doi.org/10.31557/APJCP.2021.22.S1.9 DOI: https://doi.org/10.31557/APJCP.2021.22.S1.9
[250] J. Zafari, H. Vazini, F. Javani-jouni, P. Abdolmaleki, R. Monajemi, E. Shams, M. Satari. Anticancer Effects of Moderate Static Magnetic Field on Cancer Cells in Vitro. Research in Molecular Medicine 6 (2018) 54-64. https://doi.org/10.18502/rmm.v6i3.4610 DOI: https://doi.org/10.18502/rmm.v6i3.4610
[251] S.I. Jenkins, M.R. Pickard, N. Granger, D.M. Chari. Magnetic nanoparticle-mediated gene transfer to oligodendrocyte precursor cell transplant populations is enhanced by magnetofection strategies. ACS Nano 5 (2011) 6527-6538. https://doi.org/10.1021/NN2018717 DOI: https://doi.org/10.1021/nn2018717
[252] H. Potter, R. Heller. Transfection by Electroporation. Current Protocols in Molecular Biology 121 (2018) 9.3.1-9.3.13. https://doi.org/10.1002/cpmb.48 DOI: https://doi.org/10.1002/cpmb.48
[253] T. Kotnik, L. Rems, M. Tarek, D. Miklavcic. Membrane Electroporation and Electropermeabilization: Mechanisms and Models. Annual Review of Biophysics 48 (2019) 63-91. https://doi.org/10.1146/ANNUREV-BIOPHYS-052118-115451 DOI: https://doi.org/10.1146/annurev-biophys-052118-115451
[254] E.T. Jordan, M. Collins, J. Terefe, L. Ugozzoli, T. Rubio. Optimizing electroporation conditions in primary and other difficult-to-transfect cells. Journal of Biomolecular Techniques 19 (2008) 328
[255] S. Hosseinpour, L.J. Walsh. Laser-assisted nucleic acid delivery: A systematic review. Journal of Biophotonics 14 (2021) 202000295. https://doi.org/10.1002/jbio.202000295 DOI: https://doi.org/10.1002/jbio.202000295
[256] C.-P. Yao, Z.-X. Zhang, R. Rahmanzadeh, G. Huettmann. Laser-based gene transfection and gene therapy. IEEE Transactions on Nanobioscience 7 (2008) 111-119. https://doi.org/10.1109/TNB.2008.2000742. DOI: https://doi.org/10.1109/TNB.2008.2000742
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