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Cancer-targeted and glutathione-responsive micellar carriers for controlled delivery of cabazitaxel.
Nanotechnology 2018 December 5
Novel type of multifunctional polymeric micelles (PMs) designated as HM-PMss/CTX micelles were developed in the present study for tumor-targeted and glutathione (GSH)-responsive delivery of cabazitaxel (CTX). The surface of the vehicles was modified with piloting molecules (HM-3 peptide), which targets α v β 3 integrin overexpressed on cancer cells, and the micelle core was cross-linked by GSH-disintegrable disulfide linkages for controlled drug release. HM-PMss/CTX micelles were prepared using a mixture of two functionalized amphiphilic block copolymers and found to physically encapsulate CTX with excellent entrapment efficiency (93.94 ± 4.19%), drug-loading capacity (8.39 ± 2.28%), and a narrow size distribution. In vitro release profiles showed that CTX remained stably entrapped in the micelles in a release medium without GSH or with GSH of low concentration, while undergoing a rapid release in a highly reductive environment. Cellular uptake experiments showed that the conjugation of the targeting peptide, containing an arginine-glycine-aspartate sequence, enhanced the cellular uptake of HM-PMss/CTX micelles via α v β 3 integrin-mediated endocytosis. In vitro cell viability measurements revealed that blank micelles were biocompatible, while HM-PMss/CTX micelles, owing to their tumor-targeting ability and GSH sensitivity, effectively inhibited the proliferation of MDA-MB-231 breast cancer cells. These results indicate that HM-PMss/CTX micelles could be a promising platform for future intelligent drug delivery in cancer therapy.
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