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Reduction-cleavable polymeric vesicles with efficient glutathione-mediated drug release behavior for reversing drug

Tianbin Ren1, Wei Wu, Menghong Jia

  • 1The Institute for Biomedical Engineering and Nano Science, School of Materials and Engineering, Tongji University , Shanghai 200092, P. R. China.

ACS Applied Materials & Interfaces
|October 3, 2013
PubMed

Insights

Researchers developed novel reduction-cleavable polymeric vesicles that release drugs in response to glutathione. These vesicles effectively reverse multidrug resistance in cancer cells by enhancing drug accumulation and improving chemotherapy efficacy.

Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cancer Therapy

Background:

  • Multidrug resistance (MDR) in cancer chemotherapy is a significant clinical challenge, primarily due to the overexpression of drug-efflux transporters.
  • Effective strategies are needed to overcome MDR and improve the efficacy of cancer treatment.

Purpose of the Study:

  • To design and develop reduction-cleavable polymeric vesicles for glutathione-mediated drug release.
  • To investigate the potential of these vesicles in reversing multidrug resistance in cancer cells.

Main Methods:

  • Self-assembly of triblock copolymers (disulfide-linked PEG and PzLL) into polymeric vesicles.
  • Characterization of vesicle structure using transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM).
  • Assessment of drug release kinetics (doxorubicin hydrochloride, DOX·HCl) in response to glutathione (GSH) and evaluation of cellular uptake and efficacy in drug-resistant cancer cell lines (HeLa, MDA-MB-231).

Main Results:

  • Polymeric vesicles with a distinct hollow structure were successfully synthesized.
  • Glutathione significantly accelerated DOX·HCl release from the vesicles (>3-fold).
  • Enhanced nuclear accumulation of DOX·HCl was observed in HeLa cells, and gemcitabine hydrochloride (GC·HCl)-resistant MDA-MB-231 cells showed significantly reduced viability upon treatment with GC·HCl-loaded vesicles.

Conclusions:

  • The developed reduction-cleavable vesicles demonstrate efficient glutathione-mediated drug release.
  • These vesicles show promise in overcoming multidrug resistance by enhancing intracellular drug delivery and efficacy in resistant cancer cells.

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