Alendronate Ptiv Prodrug Amphiphile for Enhanced Chemotherapy Targeting and Bone Destruction Inhibition in Osteosarcoma

Abstract Chemotherapy remains the primary treatment method for osteosarcoma after surgery. However, the lack of selectivity of chemotherapy for osteosarcoma leads to unpredictable therapeutic effects, undesirable side effects and drug resistance. A platinum(IV) (Pt IV ) prodrug amphiphile covalently bound to alendronate (ALN) and a lipid tail was designed to overcome this limitations. ALN‐Pt IV ‐Lipo could self‐assemble into Pt IV lipid nanoparticles (APt IV ) for osteosarcoma targeting chemotherapy and bone destruction inhibition. We demonstrated that APt IV achieved an 8‐fold increase in the eradication of osteosarcoma cells compared to cisplatin and 3‐fold selective inhibition of osteosarcoma cells over breast cancer cells via APt IV in vitro. After intravenous injection, APt IV effectively accumulated at the osteosarcoma site in vivo, resulting in significantly suppressed primary osteosarcoma growth (TGI = 86%), and alleviation of bone destruction. Therefore, APt IV delivered a promising solution for enhanced chemotherapy targeting and bone destruction inhibition in osteosarcoma. This article is protected by copyright. All rights reserved