Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery

Yanwu Cao, Min Gao, Chao Chen, Aiping Fan, Ju Zhang, Deling Kong, Zheng Wang, Dan Peer, Yanjun Zhao

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Nanoscale drug delivery platforms have been developed over the past four decades that have shown promising clinical results in several types of cancer and inflammatory disorders. These nanocarriers carrying therapeutic payloads are maximizing the therapeutic outcomes while minimizing adverse effects. Yet one of the major challenges facing drug developers is the dilemma of premature versus on-demand drug release, which influences the therapeutic regiment, efficacy and potential toxicity. Herein, we report on redox-sensitive polymer-drug conjugate micelles for on-demand intracellular delivery of a model active agent, curcumin. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a disulfide bond or ester bond (control), respectively. The self-assembled redox-sensitive micelles exhibited a hydrodynamic size of 115.6±5.9 (nm) with a zeta potential of -10.6±0.7 (mV). The critical micelle concentration was determined at 6.7±0.4 (μg mL-1). Under sink conditions with a mimicked redox environment (10 mM dithiothreitol), the extent of curcumin release at 48 h from disulfide bond-linked micelles was nearly three times higher compared to the control micelles. Such rapid release led to a lower half maximal inhibitory concentration (IC50) in HeLa cells at 18.5±1.4 (μg mL-1), whereas the IC50 of control micelles was 41.0±2.4 (μg mL-1). The cellular uptake study also revealed higher fluorescence intensity for redox-sensitive micelles. In conclusion, the redox-sensitive polymeric conjugate micelles could enhance curcumin delivery while avoiding premature release, and achieving on-demand release under the high glutathione concentration in the cell cytoplasm. This strategy opens new avenues for on-demand drug release of nanoscale intracellular delivery platforms that ultimately might be translated into pre-clinical and future clinical practice.

Original languageEnglish (US)
Article number115101
Issue number11
StatePublished - Mar 20 2015


  • curcumin
  • micelle
  • on-demand delivery
  • polymeric conjugate
  • redox-sensitive
  • triggered-release

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering
  • Electrical and Electronic Engineering


Dive into the research topics of 'Triggered-release polymeric conjugate micelles for on-demand intracellular drug delivery'. Together they form a unique fingerprint.

Cite this