Abstract
For cancer treatment, nanocarriers were designed with cationic lipids and polymers to improve the cytosolic delivery efficiency of siRNA. Though the positively charged nanocarriers showed great potential for RNA therapy, it was inevitable to generate the potential cytotoxicity. We constructed a pH-responsive nanoplatform, which co-carried siRNA and anticancer drug (hydroxycamptothecine, HCPT), to integrate gene therapy and chemotherapy for combination cancer therapy. The fluorescent conjugated polymer nanoparticles (CPNPs) modified with cell-penetrating peptides were employed as cores to carry siRNA molecules (siRNA-CPNPs) and track the biodistribution of nanotherapeutics by virtue of fluorescence. Calcium phosphate (CaP) nanocoatings were deposited on the surface of siRNA-CPNPs, followed by loading with HCPT and aptamers targeting cancer cells to obtain a targeted and tumor acid-responsive biocompatible nanoplatform. After the uptake of cancer cells, the CaP nanocoatings were decomposed in the acidic endo/lysosomes to release HCPT, and the siRNA-CPNPs were exposed to facilitate the siRNA endo/lysosome escape and cytoplasm delivery. Results obtained from both in vitro and in vivo studies in tumor inhibition expressed that the combined therapy exhibited a better therapeutic efficacy than any monotherapy.
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