Nanotechnology-enabled delivery of NQO1 bioactivatable drugs

Xinpeng Ma, Zachary R. Moore, Gang Huang, Xiumei Huang, David A. Boothman, Jinming Gao

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations


Current cancer chemotherapy lacks specificity and is limited by undesirable toxic side-effects, as well as a high rate of recurrence. Nanotechnology has the potential to offer paradigm-shifting solutions to improve the outcome of cancer diagnosis and therapy. β-Lapachone (β-lap) is a novel anticancer agent whose mechanism of action is highly dependent on NAD(P)H:quinone oxidoreductase 1 (NQO1), a phase II detoxifying enzyme overexpressed in solid tumors from a variety of cancer types. However, the poor water solubility of β-lap limits its clinical potential. A series of drug formulations were developed for systemic administration in preclinical evaluations. Encapsulation of β-lap into polymeric micelles showed less side-effects and higher maximum tolerated dose (MTD), prolonged blood circulation time and preferential accumulation in tumors with greatly improved safety and antitumor efficacy. The prodrug strategy of β-lap further decreases the crystallization of β-lap by introducing esterase degradable side chains to the rigid fused ring structure. β-Lap prodrugs considerably increased the stability, drug-loading content and delivery efficiency of nanoparticles. The optimized formulation of β-lap-dC3 prodrug micelles showed excellent antitumor efficacy in treating orthotopic non-small cell lung tumors that overexpress NQO1, with target validation using pharmacodynamic endpoints.

Original languageEnglish (US)
Pages (from-to)672-680
Number of pages9
JournalJournal of Drug Targeting
Issue number7-8
StatePublished - Sep 14 2015


  • Cancer targeting
  • NQO1
  • drug delivery
  • nanoparticle
  • prodrug
  • β-lapachone

ASJC Scopus subject areas

  • Pharmaceutical Science


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