Acid-Labile Copolymer Micelles Cross-Linked by a Twin Ortho Ester Cross-Linking Agent: Synthesis, Characterization, and Evaluation

摘要

In this work, a series of poly( ethylene glycol)-block-poly(N-succinimidyl methacrylate) ( PEG-b-PNSM) micelles with different length of PNSM are prepared by self-assembly in phosphate buffer. In situ cross-linked micelles ( CLM) with high stability at neutral pH are obtained by adding a pH-sensitive cross-linker bearing two five-membered ortho ester rings, 2-{4-[2-( 2-amino-ethoxy)-[1,3]dioxolan-4-ylmethoxymethyl]-[1,3]dioxolan-2-yloxy}-thylamine. Nile Red as a model drug is easily loaded into CLM, and the release rate accelerate at acidic environments ( pH 5). Cytotoxicity of PEG-b-PNSM and CLM against NIH3T3 cells is determined and favorable biocompatibility is possessed. Confocal laser scanning microscopy study shows that Nile Red-loaded CLM has excellent cellular uptake by MCF-7 cells. Paclitaxel ( PTX) is successfully encapsulated into the crosslinked micelles. In vitro cytotoxicity of free PTX, and PTX-loaded CLM causes almost the same potency in killing MCF-7 cells. These results suggest that cross-linked micelles can be a potential vehicle for delivering hydrophobic anticancer drugs to tumors.