Tumor-preferential sustained drug release enhances antitumor activity of block copolymer micelles

Andrei Ponta, Younsoo Bae

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Nanoparticles are widely used as drug carriers for controlled, tumor-targeted delivery of various anticancer agents that have biopharmaceutical limitations such as water solubility and tissue permeability. Growing evidence suggests that nanoparticles not only reduce toxic side effects of anticancer drugs but also improve the therapeutic efficacy as a function of their drug-release profile. The purpose of this study is to confirm such hypothetical effects of tunable drug release on improving antitumor activity of nanoparticles in vitro and in vivo, using block copolymer micelles as drug carriers. Micelles were prepared from poly(ethylene glycol)-poly(aspartate) block copolymers modified with hydrazide (HYD), aminobenzoate hydrazide (ABZ) and glycine hydrazide (GLY) linkers to achieve a pH-dependent, tunable release of doxorubicin (DOX), a model anticancer drug. Regardless of the drug-release profile, all three micelles showed similar properties in vitro, such as pH-dependent drug release, intracellular drug delivery and cancer cell growth inhibition. However, micelles releasing DOX slowly in vitro showed that the most effective antitumor activity in vivo, compared to the micelles releasing drugs faster. These results demonstrate that tumor-preferential sustained drug release can enhance the antitumor activity of the micelles.

Original languageEnglish
Pages (from-to)619-628
Number of pages10
JournalJournal of Drug Targeting
Issue number7
StatePublished - Aug 2014

Bibliographical note

Funding Information:
The authors report no declarations of interest. This study was supported by the Kentucky Lung Cancer Research Program. The authors acknowledge Dr Pengxiao Cao for his technical support in performing the in vivo study.


  • Acid-labile linkers
  • Doxorubicin
  • Drug delivery
  • Hydrazone
  • Nanoparticles
  • PH-controlled drug release

ASJC Scopus subject areas

  • Pharmaceutical Science


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