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Redox-Activatable ATP-Depleting Micelles with Dual Modulation Characteristics for Multidrug-Resistant Cancer Therapy

Hebin Wang1,2, Yang Li1, Miaozun Zhang3

  • 1Department of Chemistry, Zhejiang University, Hangzhou, 310028, China.

Advanced Healthcare Materials
|February 3, 2017
PubMed

Insights

A novel nanomicelle system rapidly depletes ATP in cancer cells, enhancing paclitaxel (PTX) and siRNA delivery to overcome multidrug resistance (MDR). This dual action resensitizes cancer cells, improving therapeutic outcomes against MDR tumors.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Multidrug-resistant (MDR) cancer poses a significant therapeutic challenge.
  • Existing therapies often struggle with drug efflux and limited efficacy in MDR cancer cells.

Purpose of the Study:

  • To develop a novel ATP-depleting nanomicelle system for codelivery of paclitaxel (PTX) and polo-like kinase1 (PLK1) siRNA.
  • To address MDR by preventing intracellular PTX efflux and inhibiting PLK1 expression.

Main Methods:

  • Self-assembly of a redox-responsive amphiphilic polymer (bPEG-SS-P123-PEI) into multilayered nanomicelles.
  • Codelivery of PTX and PLK1 siRNA using the nanomicelle system.
  • Evaluation of ATP depletion, drug release, and therapeutic efficacy in MDR cancer models.

Main Results:

  • The nanomicelles effectively codeliver PTX and PLK1 siRNA.
  • Intracellular redox activation triggers rapid ATP depletion, inhibiting PTX efflux.
  • Combined ATP depletion and siRNA inhibition resensitized MDR cancer cells, enhancing PTX efficacy.
  • Significant reduction in tumor growth was observed in vivo.

Conclusions:

  • The developed ATP-depleting nanomicelle system offers an innovative strategy for dual modulation of cancer MDR.
  • This approach provides spatial and temporal control for enhanced cancer therapy.
  • The codelivery of PTX and PLK1 siRNA demonstrates potent synergistic effects against MDR tumors.
Keywords:
PEGylationanticancer drug deliverycombination therapynanomedicinestimuli-responsive polymeric micelles

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