Surface-Engineered Porous Silicon Nanoparticles for Targeted Osteosarcoma Therapy

Osteosarcoma, an aggressive primary bone cancer, poses significant clinical challenges due to limited treatment options. Targeted nanocarriers have emerged as a promising strategy to facilitate the precise delivery of chemotherapeutics to deeply seated tissues like bone. In this study, we developed a bone-targeted nanocarrier for doxorubicin delivery using alendronate-conjugated poly(N-(2-hydroxypropyl)acrylamide) (ALN-PolyHPAm)-functionalized porous silicon nanoparticles. These tailored nanoparticles, featuring hydrophobic pores, showed a high drug-loading capacity and sustained, pH-responsive doxorubicin release. The alendronate-decorated PolyHPAm@D-pSiNPs displayed excellent antifouling properties while maintaining a strong hydroxyapatite-binding affinity in a hydroxyapatite-coated quartz crystal microbalance sensor; they also exhibited high cell association in human osteosarcoma cells (Saos-2) and selective binding to hydroxyapatite in a mineralized cell assay. Furthermore, doxorubicin-loaded ALN-PolyHPAm@D-pSiNPs displayed significantly higher in vitro cytotoxicity in Saos-2 cells compared to doxorubicin-loaded nontargeted PolyHPAm@D-pSiNPs and free doxorubicin. This developed bone-targeted pSiNP platform holds significant promise for the targeted osteosarcoma treatment.