Bone-targeted stimuli-responsive polymeric nanocarriers for osteosarcoma treatment

Abstract

Osteosarcoma, a highly aggressive bone tumor commonly diagnosed in adolescence, has major treatment challenges due to metastasis and chemoresistance. This study presents the development of bone-targeted, pH-sensitive polymeric dual drug delivery systems based on a triblock copolymer, P(BPMA-b-OEGMEMA-b-FPMA), synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. After deprotection of the BPMA segments, the chemotherapeutic agent doxorubicin (Dox) and/or the bone-targeting drug alendronate (Aln) were loaded onto the polymer, resulting in self-assembled nanomicelles. Dynamic light scattering (DLS) analysis showed that the hydrodynamic diameters of the Dox-loaded (M1), Aln-loaded (M2), and dual drug-loaded (M3) micelles were approximately 100.00 +/- 6.34 nm, 97.70 +/- 4.39 nm, and 89.86 +/- 4.77 nm, respectively, with narrow size distributions. In vitro cytotoxicity assays demonstrated that the dual-loaded micelles (M3) exhibited significantly higher selective toxicity against SAOS-2 osteosarcoma cells compared to free drugs, while maintaining low toxicity toward healthy HUVEC endothelial cells. Cellular uptake studies confirmed enhanced internalization of the bone-targeted nanocarriers by SAOS-2 cells. These findings highlight the potential of this novel polymeric system to improve therapeutic outcomes by effectively targeting bone tumor cells and minimizing side effects through controlled and selective drug delivery.