Fabrication of anionic dextran-coated micelles for aptamer targeted delivery of camptothecin and survivin-shRNA to colon adenocarcinoma.

ABSTRACT

In this study, we synthesized PLA-PEI micelles which was co-loaded with an anticancer drug, camptothecin (CPT), and survivin-shRNA (sur-shRNA). The hydrophobic CPT was encapsulated in the core of the polymeric micelles while sur-shRNA was adsorbed on the shell of the cationic micelles. Then, the positively-charged sur-shRNA-loaded micelles were coated with poly carboxylic acid dextran (PCAD) to form PLA/PEI-CPT-SUR-DEX. To selectively target the system to colon cancer cells, AS1411 aptamer was covalently attached to the surface of the PCAD-coated nanoparticles (PLA/PEI-CPT-SUR-DEX-APT). PLA/PEI-CPT-SUR-DEX-APT enhanced cellular uptake through receptor-mediated endocytosis followed by increased CPT accumulation, downregulation of survivin, and thereby 38% cell apoptosis. In C26 tumor-bearing mice models, after administered intravenously, PLA/PEI-CPT-SUR-DEX-APT and PLA/PEI-CPT-SUR-DEX formulations resulted in a significant inhibition of the tumor growth with tumor inhibition rate of 93% and 87%, respectively. Therefore, PLA/PEI-CPT-SUR-DEX-APT could be a versatile co-delivery vehicle for promising therapy of colorectal cancer.