Polymers prepared through an "ATRP polymerization-esterification" strategy for dual temperature- and reduction-induced paclitaxel delivery.

Abstract

Clinically, the nanotherapy of tumors has been limited by the drug content, efficiency of targeted release, and bioavailability. In this study, we fabricated an amphiphilic block polymer, poly(2-methacryloyloxyethyl thiocticcarboxylate)-block-poly(N-isopropylacrylamide) (PMAOETC-b-PNIPAM), using an “ATRP polymerization–esterification” strategy for paclitaxel (PTX) delivery. The hydrophobic drug paclitaxel was encapsulated based on hydrogen bond interactions between PTX and the PMAOETC and PNIPAM blocks, together with hydrophobic interactions between PTX and PMAOETC segments, affording PTX-laden polymer micelles with ∼30% drug loading content. The critical micelle concentration of the PTX-loaded polymeric micellar aggregates was 34.53 mg l−1, as determined through fluorescence spectroscopy, which indicated favorable stability during infinite dilution by body fluids. The phase transition temperature of the micelles was tunable (36.10–39.48 °C) via adjusting the lengths of the blocks. The PTX-laden micelles showed the release of a significant amount of PTX in cancerous tissue, while negligible cytotoxicity was shown against HCT-116 cells in PBS at pH 7.4 and 37 °C. Further in vivo anticancer studies revealed that antitumor treatment using the PTX-laden micelles caused a significant suppression in tumor volume compared with a free-PTX-treated group. This study provides a reference for improving drug content levels and optimizing the therapeutic effects of drug delivery systems from the perspective of polymer preparation.