Redox-Responsive Core-Cross-Linked Block Copolymer Micelles for Overcoming Multidrug Resistance in Cancer Cells

• DOI: 10.1021/acsami.7b18245
• Publication Date: 2018-01-22T11:18:31Z
• Authors: Chiranjit Maiti; Sheetal Parida; Shibayan Kayal; Saikat Maiti; Mahitosh Mandal; Dibakar Dhara
• Keywords: Nanocarriers

Success of chemotherapy as a treatment for cancer has been often inhibited by multidrug resistance (MDR) the cells. There is clear need to generate strategies overcome this resistance. In work, we have developed redox-responsive and core-cross-linked micellar nanocarriers using poly(ethylene glycol)-block-poly(2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate) diblock copolymers (PEG-b-PLAHEMA) with tunable swelling properties delivery drugs toward drug-sensitive MDA-MB-231 drug-resistant (231R) PEG-b-PLAHEMA containing varying number 2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate (LAHEMA) units were synthesized employing reversible addition-fragmentation chain transfer polymerization technique. The block copolymer self-assembly, cross-linking induced reduction, de-cross-linking triggered time-dependent controlled micelles studied dynamic light scattering, fluorescence spectroscopy, transmission electron microscopy. vitro cytotoxicity, cellular uptake efficiency, glutathione-responsive anticancer activity doxorubicin (DOX) encapsulated in (CCMs) both cell lines evaluated. Significant reduction IC50 was observed DOX-loaded CCMs 231R lines, which further improved coencapsulating DOX verapamil (a P-glycoprotein inhibitor) CCMs. Thus, these reduction-sensitive biocompatible property are very promising overcoming MDR