Tuneable carbon dots coated iron oxide nanoparticles as superior T1 contrast agent for multimodal imaging: Original scientific arfticle

Anbazhagan Thirumalai; Palani  Sharmiladevi; Koyeli  Girigoswami; Alex Daniel  Prabhu; Agnishwar Girigoswami

doi:10.5599/admet.2790

Authors

Anbazhagan Thirumalai Medical Bionanotechnology, Faculty of Allied Health Sciences (FAHS), Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, TN-603103, India. https://orcid.org/0000-0002-2659-5191
Palani Sharmiladevi Medical Bionanotechnology, Faculty of Allied Health Sciences (FAHS), Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, TN-603103, India. https://orcid.org/0000-0001-7283-5400
Koyeli Girigoswami Medical Bionanotechnology Lab, Depatment of Obstetrics and Gynaecology, Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, 602105, India https://orcid.org/0000-0003-1554-5241
Alex Daniel Prabhu Department of Radiology, Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, TN-603103, India. https://orcid.org/0000-0002-0474-4352
Agnishwar Girigoswami Medical Bionanotechnology, Faculty of Allied Health Sciences (FAHS), Chettinad Hospital & Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, TN-603103, India https://orcid.org/0000-0003-0475-2544

DOI:

https://doi.org/10.5599/admet.2790

Keywords:

Magnetic nanoparticles, super paramagnetic iron oxide nanoparticles, hydrothermal method, T1 weighted magnetic resonance imaging, fluorescence imaging, diagnosis

Abstract

Background and purpose: Multifunctional hybrid nanoparticles garner heightened interest for prospective biomedical applications, including medical imaging and medication administration, owing to their synergistic benefits of constituent components. Therefore, we demonstrated an optimized protocol for synthesizing magnetofluorescent nanohybrids comprising fluorescent carbon dots with magnetic nanoparticles. Experimental approach: Carbon dot-coated iron oxide nanoparticles (CDs@Fe₂O₃) were synthesized with varying citric acid concentrations by a one-pot hydrothermal synthesis method for the development of a low-cost and biocompatible contrast agent (CA) for enhanced multimodal imaging (fluorescent and T₁ and T₂ weighted magnetic resonance imaging (MRI)) to replace the conventional CAs. Key results: The physicochemical characterization of the synthesized CDs@Fe₂O₃ revealed that 3 g of citric acid used for the synthesis of nanoparticles, keeping Fe(II) and Fe(III) ratio 1:2 provides higher stability of -78 mV zeta potential, saturation magnetization of 24 emu/g, with a hydrodynamic diameter of 68 nm. Carbon coating affects surface spins on Fe₂O₃, resulting in fewer surface-based relaxation centres, making T₁ relaxation relatively more prominent. Furthermore, the surface-engineered iron oxide NPs are efficient in producing both T₁ and T₂ weighted MRI as well as fluorescence-based imaging. The molar relaxivity and molar radiant efficiency derived from phantom studies demonstrate their effectiveness in multimodal medical imaging. The cytotoxicity assay, haemolysis assay, haematology, and histopathology studies show that the optimized CDs@Fe₂O₃ are biocompatible, haemocompatible, and negligibly toxic. Conclusion: We can conclude the significant potency of CDs@Fe₂O₃ for multimodal diagnosis.

Downloads

Download data is not yet available.

References

[1] D.A. Fernandes. Review on metal-based theranostic nanoparticles for cancer therapy and imaging. Technology in Cancer Research & Treatment 22 (2023) 15330338231191493. https://doi.org/10.1177/15330338231191493

[2] D.A. Fernandes. Review on iron nanoparticles for cancer theranostics: synthesis, modification, characterization and applications. Journal of Nanoparticle Research 25 (2023) 170. https://doi.org/10.1007/s11051-023-05807-1

[3] K. Girigoswami, P. Pallavi, A. Girigoswami. Intricate subcellular journey of nanoparticles to the enigmatic domains of endoplasmic reticulum. Drug Delivery 30 (2023) 2284684. https://doi.org/10.1080/10717544.2023.2284684

[4] K. Elumalai, S. Srinivasan, A. Shanmugam. Review of the efficacy of nanoparticle-based drug delivery systems for cancer treatment. Biomedical Technology 5 (2024) 109-122. https://doi.org/10.1016/j.bmt.2023.09.001

[5] K. Harini, K. Girigoswami, P. Pallavi, P. Gowtham, A. Thirumalai, K. Charulekha, A. Girigoswami. MoS2 nanocomposites for biomolecular sensing, disease monitoring, and therapeutic applications. Nano Futures 7 (2023) 032001. https://doi.org/10.1088/2399-1984/ace178

[6] S.W. Vedakumari, R. Senthil, S. Sekar, C.S. Babu, T.P. Sastry. Enhancing anti-cancer activity of erlotinib by antibody conjugated nanofibrin - In vitro studies on lung adenocarcinoma cell lines. Materials Chemistry and Physics 224 (2019) 328-333. https://doi.org/10.1016/j.matchemphys.2018.11.061

[7] J. Affrald R, N. M, S. Narayan. A comprehensive review of manganese dioxide nanoparticles and strategy to overcome toxicity. Nanomedicine Journal 10 (2023) 1-15. https://doi.org/10.22038/nmj.2022.66131.1694

[8] K. Wu, D. Su, J. Liu, R. Saha, J.-P. Wang. Magnetic nanoparticles in nanomedicine: a review of recent advances. Nanotechnology 30 (2019) 502003. https://doi.org/10.1088/1361-6528/ab4241

[9] M.I. Anik, M.K. Hossain, I. Hossain, A.M.U.B. Mahfuz, M.T. Rahman, I. Ahmed. Recent progress of magnetic nanoparticles in biomedical applications: A review. Nano Select 2 (2021) 1146-1186. https://doi.org/10.1002/nano.202000162

[10] S. Khizar, N.M. Ahmad, N. Zine, N. Jaffrezic-Renault, A. Errachid-el-salhi, A. Elaissari. Magnetic Nanoparticles: From Synthesis to Theranostic Applications. ACS Applied Nano Materials 4 (2021) 4284-4306. https://doi.org/10.1021/acsanm.1c00852

[11] K. Harini, K. Girigoswami, P. Pallavi, P. Gowtham, A.D. Prabhu, A. Girigoswami. Advancement of magnetic particle imaging in diagnosis and therapy. Advances in Natural Sciences: Nanoscience and Nanotechnology 15 (2024) 023002. https://doi.org/10.1088/2043-6262/ad3b7a

[12] C. Comanescu. Magnetic Nanoparticles: Current Advances in Nanomedicine, Drug Delivery and MRI. Chemistry 4 (2022) 872-930. https://doi.org/10.3390/chemistry4030063

[13] R. Dubey, N. Sinha, N.R. Jagannathan. Potential of in vitro nuclear magnetic resonance of biofluids and tissues in clinical research. NMR in Biomedicine 36 (2023) e4686. https://doi.org/10.1002/nbm.4686

[14] V. Haribabu, K. Girigoswami, A. Girigoswami. Magneto-silver core–shell nanohybrids for theragnosis. Nano-Structures & Nano-Objects 25 (2021) 100636. https://doi.org/10.1016/j.nanoso.2020.100636

[15] S.B. Joga, D. Korabandi, S.K. Lakkaboyana, V. Kumar. Synthesis of iron nanoparticles on lemon peel carbon dots (LP-CDs@Fe3O4) applied in Photo-Catalysis, Antioxidant, Antidiabetic, and Hemolytic activity. Inorganic Chemistry Communications 174 (2025) 113960. https://doi.org/10.1016/j.inoche.2025.113960

[16] H. Perumalsamy, S.R. Balusamy, J. Sukweenadhi, S. Nag, D. MubarakAli, M. El-Agamy Farh, H. Vijay, S. Rahimi. A comprehensive review on Moringa oleifera nanoparticles: importance of polyphenols in nanoparticle synthesis, nanoparticle efficacy and their applications. Journal of nanobiotechnology 22 (2024) 71. https://doi.org/10.1186/s12951-024-02332-8

[17] S. Kumar, M. Kumar, A. Singh. Synthesis and characterization of iron oxide nanoparticles (Fe2O3, Fe3O4): a brief review. Contemporary Physics 62 (2021) 144-164. https://doi.org/10.1080/00107514.2022.2080910

[18] P. Farinha, J.M.P. Coelho, C.P. Reis, M.M. Gaspar. A Comprehensive Updated Review on Magnetic Nanoparticles in Diagnostics. Nanomaterials 11 (2021) 3432. https://doi.org/10.3390/nano11123432

[19] A.C. Anselmo, S. Mitragotri. Nanoparticles in the clinic. Bioengineering & translational medicine 1 (2016) 10-29. https://doi.org/10.1002/btm2.10003

[20] P. Chauhan, P. Kushwaha. Applications of Iron Oxide Nanoparticles in Magnetic Resonance Imaging (MRI). Nanoscience & Nanotechnology-Asia 11 (2021) 290-299. https://doi.org/10.2174/2210681210999200728102036

[21] D.K. Dwivedi, N.R. Jagannathan. Emerging MR methods for improved diagnosis of prostate cancer by multiparametric MRI. Magnetic Resonance Materials in Physics, Biology and Medicine 35 (2022) 587-608. https://doi.org/10.1007/s10334-022-01031-5

[22] V. Haribabu, P. Sharmiladevi, N. Akhtar, A.S. Farook, K. Girigoswami, A. Girigoswami. Label Free Ultrasmall Fluoromagnetic Ferrite-clusters for Targeted Cancer Imaging and Drug Delivery. Current Drug Delivery 16 (2019) 233-241. https://doi.org/10.2174/1567201816666181119112410

[23] N. Iyad, M. S.Ahmad, S.G. Alkhatib, M. Hjouj. Gadolinium contrast agents- challenges and opportunities of a multidisciplinary approach: Literature review. European Journal of Radiology Open 11 (2023) 100503. https://doi.org/10.1016/j.ejro.2023.100503

[24] B. Murugesan, S. Ramanarayanan, S. Vijayarangan, K. Ram, N.R. Jagannathan, M. Sivaprakasam. A deep cascade of ensemble of dual domain networks with gradient-based T1 assistance and perceptual refinement for fast MRI reconstruction. Computerized medical imaging and graphics 91 (2021) 101942. https://doi.org/10.1016/j.compmedimag.2021.101942

[25] P. Gowtham, K. Girigoswami, A.D. Prabhu, P. Pallavi, A. Thirumalai, K. Harini, A. Girigoswami. Hydrogels of Alginate Derivative-Encased Nanodots Featuring Carbon-Coated Manganese Ferrite Cores with Gold Shells to Offer Antiangiogenesis with Multimodal Imaging-Based Theranostics. Advanced Therapeutics 7 (2024) 2400054. https://doi.org/10.1002/adtp.202400054

[26] S.I. Eguía-Eguía, L. Gildo-Ortiz, M. Pérez-González, S.A. Tomas, J.A. Arenas-Alatorre, J. Santoyo-Salazar. Magnetic domains orientation in (Fe3O4/γ-Fe2O3) nanoparticles coated by Gadolinium-diethylenetriaminepentaacetic acid (Gd3+-DTPA). Nano Express 2 (2021) 020019. https://doi.org/10.1088/2632-959X/ac0107

[27] K. Yano, T. Matsumoto, Y. Okamoto, N. Kurokawa, T. Hasebe, A. Hotta. Fabrication of Gd-DOTA-functionalized carboxylated nanodiamonds for selective MR imaging (MRI) of the lymphatic system. Nanotechnology 32 (2021) 235102. https://doi.org/10.1088/1361-6528/abeb9c

[28] V. Frantellizzi, M. Conte, M. Pontico, A. Pani, R. Pani, G. De Vincentis. New Frontiers in Molecular Imaging with Superparamagnetic Iron Oxide Nanoparticles (SPIONs): Efficacy, Toxicity, and Future Applications. Nuclear Medicine and Molecular Imaging 54 (2020) 65-80. https://doi.org/10.1007/s13139-020-00635-w

[29] Y. Bao, J. Sherwood, Z. Sun. Magnetic iron oxide nanoparticles as T 1 contrast agents for magnetic resonance imaging. Journal of Materials Chemistry C 6 (2018) 1280-1290. https://doi.org/10.1039/C7TC05854C

[30] H. Kothandaraman, A. Kaliyamoorthy, A. Rajaram, C.R. Kalaiselvan, N.K. Sahu, P. Govindasamy, M. Rajaram. Functionalization and Haemolytic analysis of pure superparamagnetic magnetite nanoparticle for hyperthermia application. Journal of Biological Physics 48 (2022) 383-397. https://doi.org/10.1007/s10867-022-09614-y

[31] Y.-X.J. Wang. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging. World journal of gastroenterology 21 (2015) 13400. https://doi.org/10.3748/wjg.v21.i47.13400

[32] I. Fernández-Barahona, M. Muñoz-Hernando, J. Ruiz-Cabello, F. Herranz, J. Pellico. Iron Oxide Nanoparticles: An Alternative for Positive Contrast in Magnetic Resonance Imaging. Inorganics 8 (2020) 28. https://doi.org/10.3390/inorganics8040028

[33] D. Ling, T. Hyeon. Chemical design of biocompatible iron oxide nanoparticles for medical applications. Small 9 (2013) 1450-1466. https://doi.org/10.1002/smll.201202111

[34] J.R. Vargas-Ortiz, C. Gonzalez, K. Esquivel. Magnetic Iron Nanoparticles: Synthesis, Surface Enhancements, and Biological Challenges. Processes 10 (2022) 2282. https://doi.org/10.3390/pr10112282

[35] R.J. Affrald, S.P.N. Banu, D. Arjunan, K.A. Selvamani, S. Narayan. Synthesis and Characterisation of Alginate Functionalized Gold Nanoparticles for Melamine Detection. BioNanoScience 13 (2023) 145-152. https://doi.org/10.1007/s12668-022-01050-5

[36] P. Sharmiladevi, N. Akhtar, V. Haribabu, K. Girigoswami, S. Chattopadhyay, A. Girigoswami. Excitation wavelength independent carbon-decorated ferrite nanodots for multimodal diagnosis and stimuli responsive therapy. ACS Applied Bio Materials 2 (2019) 1634-1642. https://doi.org/10.1021/acsabm.9b00039

[37] C.F.G.C. Geraldes. Rational Design of Magnetic Nanoparticles as T1–T2 Dual-Mode MRI Contrast Agents. Molecules 29 (2024) 1352. https://doi.org/10.3390/molecules29061352

[38] H. Yue, D. Zhao, T. Tegafaw, M.Y. Ahmad, A.K. Saidi, Y. Liu, H. Cha, B.W. Yang, K.S. Chae, S.-W. Nam, Y. Chang, G.H. Lee. Core-Shell Fe3O4@C Nanoparticles as Highly Effective T2 Magnetic Resonance Imaging Contrast Agents: In Vitro and In Vivo Studies. Nanomaterials 14 (2024) 177. https://doi.org/10.3390/nano14020177

[39] P. Gowtham, K. Girigoswami, P. Pallavi, K. Harini, I. Gurubharath, A. Girigoswami. Alginate-Derivative Encapsulated Carbon Coated Manganese-Ferrite Nanodots for Multimodal Medical Imaging. Pharmaceutics 14 (2022) 2550. https://doi.org/10.3390/pharmaceutics14122550

[40] P. Sharmiladevi, V. Haribabu, K. Girigoswami, A. Sulaiman Farook, A. Girigoswami. Effect of Mesoporous Nano Water Reservoir on MR Relaxivity. Scientific reports 7 (2017) 11179. https://doi.org/10.1038/s41598-017-11710-2

[41] L. Li, K. Mak, C. Leung, K. Chan, W. Chan, W. Zhong, P. Pong. Effect of synthesis conditions on the properties of citric-acid coated iron oxide nanoparticles. Microelectronic Engineering 110 (2013) 329-334. https://doi.org/10.1016/j.mee.2013.02.045

[42] B. Jiang, Y. Tang, Y. Qu, J.-Q. Wang, Y. Xie, C. Tian, W. Zhou, H. Fu. Thin carbon layer coated Ti3+-TiO2 nanocrystallites for visible-light driven photocatalysis. Nanoscale 7 (2015) 5035-5045. https://doi.org/10.1039/C5NR00032G

[43] X. Liu, L. He, G. Han, J. Sheng, Y. Yu, W. Yang. Design of rich defects carbon coated MnFe2O4/LaMnO3/LaFeO3 heterostructure nanocomposites for broadband electromagnetic wave absorption. Chemical Engineering Journal 476 (2023) 146199. https://doi.org/10.1016/j.cej.2023.146199

[44] X. Chen, Y. Zhou, H. Han, X. Wang, L. Zhou, Z. Yi, Z. Fu, X. Wu, G. Li, L. Zeng. Optical and magnetic properties of small-size core–shell Fe3O4@C nanoparticles. Materials today chemistry 22 (2021) 100556. https://doi.org/10.1016/j.mtchem.2021.100556

[45] D. Caruntu, G. Caruntu, C.J. O'Connor. Magnetic properties of variable-sized Fe3O4 nanoparticles synthesized from non-aqueous homogeneous solutions of polyols. Journal of Physics D: Applied Physics 40 (2007) 5801. https://doi.org/10.1088/0022-3727/40/19/001

[46] S. Chaudhary, A. Umar, K. Bhasin, S. Singh. Applications of carbon dots in nanomedicine. Journal of Biomedical Nanotechnology 13 (2017) 591-637. https://doi.org/10.1166/jbn.2017.2390

[47] A. Thirumalai, K. Girigoswami, A.D. Prabhu, P. Durgadevi, V. Kiran, A. Girigoswami. 8-Anilino-1-naphthalenesulfonate-Conjugated Carbon-Coated Ferrite Nanodots for Fluoromagnetic Imaging, Smart Drug Delivery, and Biomolecular Sensing. Pharmaceutics 16 (2024) 1378. https://doi.org/10.3390/pharmaceutics16111378

[48] V. Haribabu, K. Girigoswami, P. Sharmiladevi, A. Girigoswami. Water–Nanomaterial Interaction to Escalate Twin-Mode Magnetic Resonance Imaging. ACS Biomaterials Science & Engineering 6 (2020) 4377-4389. https://doi.org/10.1021/acsbiomaterials.0c00409

[49] P. Gowtham, K. Harini, A. Thirumalai, P. Pallavi, K. Girigoswami, A. Girigoswami. Synthetic routes to theranostic applications of carbon-based quantum dots. ADMET and DMPK 11 (2023) 457–485. https://doi.org/10.5599/admet.1747

[50] A. Abou Elfadl, A.M.M. Ibrahim, A.M. El Sayed, S. Saber, S. Elnaggar, I.M. Ibrahim. Influence of α-Fe2O3, CuO and GO 2D nano-fillers on the structure, physical properties and antifungal activity of Na-CMC–PAAm blend. Scientific reports 13 (2023) 12358. https://doi.org/10.1038/s41598-023-39056-y

[51] Y. Yan, H. Tang, F. Wu, R. Wang, M. Pan. One-step self-assembly synthesis α-Fe2O3 with carbon-coated nanoparticles for stabilized and enhanced supercapacitors electrode. Energies 10 (2017) 1296. https://doi.org/10.3390/en10091296

[52] M. Qasim, A.M. Iqbal, M.T. Khan, M.A. Ghanem. Nanostructural Modification of Fe2O3 Nanoparticles: Carbon Coating for Enhanced Magnetic Behavior. physica status solidi (RRL)–Rapid Research Letters (2025) 2400230. https://doi.org/10.1002/pssr.202400230

[53] M. Moeni, M. Edokali, M. Rogers, O. Cespedes, L. Tliba, T. Habib, R. Menzel, A. Hassanpour. Effect of reaction and post-treatment conditions on physico-chemical properties of magnetic iron oxide nano-particles. Particuology 91 (2024) 155-167. https://doi.org/10.1016/j.partic.2024.02.006

[54] R. Ludmerczki, S. Mura, C.M. Carbonaro, I.M. Mandity, M. Carraro, N. Senes, S. Garroni, G. Granozzi, L. Calvillo, S. Marras. Carbon dots from citric acid and its intermediates formed by thermal decomposition. Chemistry–A European Journal 25 (2019) 11963-11974. https://doi.org/10.1002/chem.201902497

[55] W. Kasprzyk, T. Świergosz, S. Bednarz, K. Walas, N.V. Bashmakova, D. Bogdał. Luminescence phenomena of carbon dots derived from citric acid and urea – a molecular insight. Nanoscale 10 (2018) 13889-13894. https://doi.org/10.1039/C8NR03602K