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Cancer-targeted and glutathione-responsive micellar carriers for controlled delivery of cabazitaxel
- Source :
- Nanotechnology. 30:055601
- Publication Year :
- 2018
- Publisher :
- IOP Publishing, 2018.
-
Abstract
- 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.
- Subjects :
- Materials science
Bioengineering
Peptide
02 engineering and technology
010402 general chemistry
Endocytosis
01 natural sciences
Micelle
chemistry.chemical_compound
Drug Delivery Systems
Cell Line, Tumor
Neoplasms
Human Umbilical Vein Endothelial Cells
Humans
General Materials Science
Viability assay
Electrical and Electronic Engineering
Micelles
chemistry.chemical_classification
Drug Carriers
Mechanical Engineering
General Chemistry
Glutathione
021001 nanoscience & nanotechnology
In vitro
0104 chemical sciences
Drug Liberation
chemistry
Mechanics of Materials
Delayed-Action Preparations
Drug delivery
Cancer cell
Biophysics
Taxoids
0210 nano-technology
Subjects
Details
- ISSN :
- 13616528 and 09574484
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Nanotechnology
- Accession number :
- edsair.doi.dedup.....39a08c4011197671ee576015e60d8e24