High cancer selectivity and improving drug release from mesoporous silica nanoparticles in the presence of human serum albumin in cisplatin, carboplatin, oxaliplatin, and oxalipalladium treatment

Abstract

In this project, drug release was examined based on the adsorption of cisplatin, carboplatin, oxaliplatin, and oxalipalladium on aminated mesoporous silica nanoparticles (N-HMSNs) and human serum albumin (HSA). These compounds were characterized by different techniques where three clinical Pt-drugs, cisplatin, carboplatin, oxaliplatin, plus oxalipalladium were loaded and investigated for release. Based on loading analysis, the loading ability of the mentioned metallodrug on N-HMSNs was dependent on the nature of the drug structure as well as hydrophobic or hydrophilic interactions. Different adsorption and release profiles were observed for all mentioned compounds via dialysis and ICP method analysis. Although the maximum to minimum loading occurred for oxalipalladium, cisplatin, and oxaliplatin to carboplatin, respectively, release from a surface with greater control belonged to carboplatin to cisplatin systems in the absence and presence of HSA to 48 h due to weak interaction for carboplatin drug. The quick release of all mentioned compounds from the protein level at high doses of the drug during chemotherapy occurred very fast within the first 6 h. In addition, the cytotoxic activity of both free drugs and drug-loaded@N-HMSNs samples on cancerous MCF-7, HCT116, A549, and normal HFF cell lines was evaluated by MTT assay. It was found that free metallodrugs exhibited more active cytotoxic behavior on both cancerous and normal cell lines than drug-loaded@N-HMSNs. Data demonstrated that the Cisplatin@N-HMSNs with SI=6.0 and 6.6 for MCF7 and HCT116 cell lines, respectively, and Oxaliplatin@N-HMSNs with SI=7.4 for HCT116 cell line can be good candidates as an anticancer drug with minimal side effects by protecting cytotoxic drugs as well as controlled release and high selectivity.