Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Jun 8;13(3):2756.
doi: 10.5599/admet.2756. eCollection 2025.

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

Mohammadmahdi Eshaghi  1 , Fariba Ganji  1 , Hossein Shaki  1 , Lobat Tayebi  2
Affiliations
Review

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

Mohammadmahdi Eshaghi et al. ADMET DMPK. .

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.

Keywords: Nanomedicine; nanomaterials; targeted drug delivery; tumour.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
(A) General chemical structure of BPs; (B) demonstration of BPs affinity for calcium ions
Figure 2.
Figure 2.
Chemical structure of (A) BP-21 (B) BP-15 (C) BP-22
Figure 3.
Figure 3.
The lower sensitivity of BG to the acidic environment compared with CP and HAp
Figure 4.
Figure 4.
(A) Chemical structure of GON-ALN, (B) demonstration of GON-ALN affinity for calcium ions
Figure 5.
Figure 5.
Strategies for Functionalizing PLGA NPs with BPs
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Chauhan M., Sun S., Tao J., Sadeghizadeh P.P., Cherian P., Junka A.F., Sodagar E., Xing L., Boeckman R.K., Jr, Srinivasan V., Yao Z., Boyce B.F. Bisphosphonates for delivering drugs to bone. British Journal of Pharmacology 178 (2021) 2008-2025 https://doi.org/10.1111/bph.15251 10.1111/bph.15251 - DOI - PMC - PubMed
    1. Rogers M.J., Mönkkönen J., Munoz M.A. Molecular mechanisms of action of bisphosphonates and new insights into their effects outside the skeleton. Bone 139 (2020) 115493 https://doi.org/10.1016/j.bone.2020.115493 10.1016/j.bone.2020.115493 - DOI - PubMed
    1. Clarke B. Normal bone anatomy and physiology. Clinical Journal of the American Society of Nephrology: CJASN 3 (2008) 131-139 https://doi.org/10.2215/CJN.04151206 10.2215/CJN.04151206 - DOI - PMC - PubMed
    1. Nancollas G.H., Tang R., Phipps R.J., Henneman Z., Gulde S., Wu W., Mangood A., Russell R.G.G., Ebetino F.H. Novel insights into actions of bisphosphonates on bone: differences in interactions with hydroxyapatite. Bone 38 (2006) 617-627 https://doi.org/10.1016/j.bone.2005.05.003 10.1016/j.bone.2005.05.003 - DOI - PubMed
    1. Chiarella E., Nisticò C., Di Vito A., Morrone H.L., Mesuraca M. Targeting of Mevalonate-Isoprenoid Pathway in Acute Myeloid Leukemia Cells by Bisphosphonate Drugs. Biomedicines 10 (2022) 1146 https://doi.org/10.3390/biomedicines10051146 10.3390/biomedicines10051146 - DOI - PMC - PubMed

LinkOut - more resources