Targeting bone in cancer therapy: Advances and challenges of bisphosphonate-based drug delivery systems: Review article

Fariba Ganji; Mohammadmahdi Eshaghi; Hossein Shaki; Lobat Tayebi

doi:10.5599/admet.2756

Authors

Fariba Ganji Biomedical Engineering Group, Faculty of Chemical Engineering, Tarbiat Modares University, P.O.Box: 14115-143, Tehran, Iran https://orcid.org/0000-0003-0714-5213
Mohammadmahdi Eshaghi Biomedical Engineering Group, Faculty of Chemical Engineering, Tarbiat Modares University, P.O.Box: 14115-143, Tehran, Iran https://orcid.org/0000-0003-1612-6989
Hossein Shaki Biomedical Engineering Group, Faculty of Chemical Engineering, Tarbiat Modares University, P.O.Box: 14115-143, Tehran, Iran https://orcid.org/0000-0002-1349-6039
Lobat Tayebi Institute for Engineering in Medicine, Health, & Human Performance (EnMed), Batten College of Engineering and Technology, Old Dominion University, Norfolk, VA, 23529, USA https://orcid.org/0000-0003-1947-5658

DOI:

https://doi.org/10.5599/admet.2756

Keywords:

Nanomedicine, tumour, targeted drug delivery, nanomaterials

Abstract

Background and Purpose: Bisphosphonates (BPs) are well-known for their strong affinity toward bone mineral matrices and are widely used to inhibit excessive osteoclast activity associated with various bone disorders. Beyond their clinical use, their unique bone-targeting capability has positioned them as promising ligands for drug delivery systems aimed at treating bone-related cancers. Approach: The review analyses published studies on BP-functionalized drug delivery systems, including direct drug conjugates, calcium-based nanomaterials, carbon-based nanostructures, and self-assembling systems such as micelles and liposomes. In vitro assays (e.g. hydroxyapatite binding, cell viability) and in vivo biodistribution studies are discussed to evaluate targeting efficiency and therapeutic outcomes. The impact of BP structure, linker chemistry, and carrier material on drug release and bone accumulation is examined. Key Results: BP-functionalized systems consistently demonstrate improved bone targeting and enhanced drug accumulation at tumour sites compared to non-targeted approaches. Both direct conjugates and nanocarrier-based systems show promising results, with some formulations offering controlled drug release and reduced systemic toxicity. Despite these advances, certain challenges such as burst release and incomplete clinical validation remain. Conclusion: This review highlights the significant progress in BP-based drug delivery platforms for bone cancer therapy, demonstrating their potential to concentrate therapeutic agents at bone tumour sites while minimizing off-target effects. The integration of nanotechnology with BP targeting offers new opportunities for treating bone metastases and primary bone tumours. However, further research is needed to address current limitations and translate these findings into clinical practice.

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