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In this study, topotecan-loaded mesoporous silica nanoparticles were prepared and surface conjugated with folic acid (FTMN) to enhance the therapeutic efficacy of topotecan for the treatment of retinoblastoma (RB) cancers. The particles were nano-sized and exhibited a sustained release of drug in the physiological conditions. The folic acid-conjugated nanoformulations exhibited a remarkable uptake in RB cells compared to that of non-targeted nanoparticles. These results clearly indicate that receptor-mediated endocytosis is the mechanism of cellular internalization. The greater cellular uptake of FTMN resulted in significantly higher cytotoxic effect in Y79 cancer cells compared to that of other formulations. The results were well corroborated with the live/dead assay and nuclear fragmentation assay. FTMN consistently induced apoptosis of cancer cells with an efficiency of ~58%. Our results clearly showed that nanoparticulate encapsulation of TPT exhibited superior anticancer efficacy in Y79 cancer cells compared to that of free drug or non-targeted nanoparticles. As expected, FTMN exhibited a remarkable reduction in the overall tumor volume compared to any other group with less presence of tumor cells in histology staining. Overall, folic acid-conjugated nanoparticulate system could provide an effective platform for RB treatment.

Folic acid-conjugated mesoporous silica nanoparticles for enhanced therapeutic efficacy of topotecan in retina cancers