Methotrexate-F127 conjugated mesoporous zinc hydroxyapatite as an efficient drug delivery system for overcoming chemotherapy resistance in osteosarcoma cells

In this study, mesoporous zinc-substituted hydroxyapatite has been synthesized and served as a drug delivery vehicle owing to its biocompatibility and high drug loading capacity. The mesoporous nanoparticles were decorated with F127 and subsequently conjugated with methotrexate (MTX) through a stable amide linkage. Since folate receptors are overexpressed on many tumor cell surfaces, MTX on the nanocarrier system plays a dual role as a targeting molecule and a chemotherapeutic drug. The evaluation of the drug release profile revealed that MTX was cleaved from the nanoparticles by a certain type of enzyme under low pH conditions that are meant to simulate the intracellular conditions in the lysosome. Cell viability studies on primary osteosarcoma cells (Saos-2) and MTX-resistance cell lines (RSaos-2/MTX) revealed that the drug-loaded nanoparticles possess high antitumor efficacy on both of the cell lines relative to free MTX. It was also found that the inhibition of P-glycoproteins by F127 and the release of Zn2+ ions from the nanoparticles in an acidic environment effectively potentiate the antitumor efficacy of the drug-loaded nanoparticles, leading to caspase-mediated cell death. Based on these data, MTX-F127@ZnHAP nanoparticles are pH-responsive nanocarriers with precise controlled drug release and targeting effect. Therefore, they are considered to be promising candidates capable of overcoming resistance in osteosarcoma cells. Graphical abstract
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research