Abstract
A targeted anticancer prodrug system was fabricated with 180 nm mesoporous silicananoparticles (MSNs) as carriers. The anticancer drug doxorubicin (DOX) wasconjugated to the particles through an acid-sensitive carboxylic hydrazone linker whichis cleavable under acidic conditions. Moreover, folic acid (FA) was covalentlyconjugated to the particle surface as the targeting ligand for folate receptors (FRs)overexpressed in some cancer cells. The in vitro release profiles of DOX from theMSN-based prodrug systems showed a strong dependence on the environmentalpH values. The fluorescent dye FITC was incorporated in the MSNs so as totrace the cellular uptake on a fluorescence microscope. Cellular uptakes by HeLa,A549 and L929 cell lines were tested for FA-conjugated MSNs and plain MSNsrespectively, and a much more efficient uptake by FR-positive cancer cells (HeLa)can be achieved by conjugation of folic acid onto the particles because of thefolate-receptor-mediated endocytosis. The cytotoxicities for the FA-conjugated MSNprodrug, the plain MSN prodrug and free DOX against three cell lines were determined,and the result indicates that the FA-conjugated MSN prodrug exhibits highercytotoxicity to FR-positive cells, and reduced cytotoxicity to FR-negative cells. Thus,with 180 nm MSNs as the carriers for the prodrug system, good drug loading,selective targeting and sustained release of drug molecules within targeted cancercells can be realized. This study may provide useful insights for designing andimproving the applicability of MSNs in targeted anticancer prodrug systems.
Published Version
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