SBA-15 nanostructures enable tumor-selective delivery of Ph₄Sn with enhanced anticancer activity in melanoma models

Alkylarylorganotin compounds, Ph_nHex_4-nSn (n = 0-4), were prepared, characterized and immobilized into mesoporous nanostructured silica SBA-15. SBA-15 loaded with Ph₄Sn (SBA-15|Ph₄Sn) showed markedly enhanced antiproliferative activity against B16 and A375 melanoma cells with a >50-fold increase in potency in comparison to its organotin counterpart, demonstrating that SBA-15 significantly enhances the antitumor activity of Ph₄Sn. Moreover, SBA-15 increased selectivity toward cancer cells, while free Ph₄Sn affected the viability of peritoneal exudate cells (PECs) as well as primary cell line IMLEC. Both free and immobilized Ph₄Sn suppressed the division rate of melanoma cells along with an activation of Bax and Bim mediated proapoptotic signaling pathway, supported by molecular docking studies, leading to caspase-dependent apoptosis. A significant reduction in tumor size in melanoma syngeneic model induced by s.c. inoculation of B16 cells in C57BL/6 mice revealed superior therapeutic performance of immobilized tetraphenyltin(IV) in comparison to the free compound with no observable systemic toxicity, in contrast to the severe side effects observed in animals treated with CP (cisplatin). Pharmacokinetic modeling further highlights the significant improvement in solubility, bioavailability, and tissue selectivity conferred by SBA-15 immobilization.