Cited by 75Nanoparticle-Based Drug DeliveryDrug Transport and Resistance MechanismsAdvanced Polymer Synthesis and Characterization

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

Maiti, Chiranjit, Parida, Sheetal, Kayal, Shibayan, Maiti, Saikat, Mandal, Mahitosh, Dhara, Dibakar·2018·ACS Applied Materials & Interfaces

Abstract

Success of chemotherapy as a treatment for cancer has been often inhibited by multidrug resistance (MDR) of the cancer cells. There is a clear need to generate strategies to overcome this resistance. In this 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 for the delivery of drugs toward drug-sensitive MDA-MB-231 and drug-resistant MDA-MB-231 (231R) cancer cells. PEG- b -PLAHEMA containing varying number of 2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate (LAHEMA) units were synthesized by employing the reversible addition-fragmentation chain transfer polymerization technique. The block copolymer self-assembly, cross-linking induced by reduction, and de-cross-linking triggered time-dependent controlled swelling of micelles were studied using dynamic light scattering, fluorescence spectroscopy, and transmission electron microscopy. In vitro cytotoxicity, cellular uptake efficiency, and glutathione-responsive anticancer activity of doxorubicin (DOX) encapsulated in core-cross-linked block copolymer micelles (CCMs) toward both drug-sensitive and drug-resistant cancer cell lines were evaluated. Significant reduction in IC 50 was observed by DOX-loaded CCMs toward drug-resistant 231R cancer cell lines, which was further improved by coencapsulating DOX and verapamil (a P-glycoprotein inhibitor) in CCMs. Thus, these reduction-sensitive biocompatible CCMs with tunable swelling property are very promising in overcoming MDR in cancer cells.

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Crossref · 10.1021/acsami.7b18245

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Authors
Maiti, C., Parida, S., Kayal, S., Maiti, S., Mandal, M., & Dhara, D.
Affiliations
Indian Institute of Technology Kharagpur (IN)
Corresponding author
Dhara, Dibakar
Venue
ACS Applied Materials & Interfaces
Published
2018-02-05
Volume
10
Issue
6
Pages
5318-5330
ISSN
  • 1944-8244 (ISSN-L)
  • 1944-8252
OpenAlex
W2785262730
Cited by
75
References
64
Citations by year
2025: 2 · 2024: 9 · 2023: 4 · 2022: 11 · 2021: 10 · 2020: 18 · 2019: 18 · 2018: 3
FWCI
3.97
Type
journal article
Language
en
Open access
closed
Locations
  • ACS Applied Materials & Interfaces (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University Grants Commission
  • Department of Science and Technology, Ministry of Science and Technology (EMR/2016/007040)
  • Indian Institute of Technology Kharagpur
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
Keywords
multidrug resistance, redox-responsive nanocarriers, glutathione-responsive drug delivery, doxorubicin, verapamil, P-glycoprotein inhibition, MDA-MB-231 cells, chemoresistance, RAFT polymerization
MeSH terms
Doxorubicin, Drug Carriers, Humans, Micelles, Oxidation-Reduction, Polyethylene Glycols, Polymers, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Cell Line, Tumor

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