Triggered release of pharmacophores from [Ni(HAsO3)]-loaded polymer-caged nanobin enhances pro-apoptotic activity: A combined experimental and theoretical study

Sang Min Lee, One Sun Lee, Thomas V. O'Halloran, George C. Schatz, Son Binh T. Nguyen

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Nanoscale drug delivery platforms can provide an attractive therapeutic strategy for cancer treatments, as they can substantially reduce the adverse side effects associated with toxic small-molecule anticancer agents. For enhanced therapeutic efficacy to be achieved with such platforms, a tumor-specific drug-release trigger is a critical requirement. This article reports the use of a pH-sensitive polymer network that surrounds a nanoscale liposome core to trigger the release of both encapsulated hydrophilic, membrane-impermeable NiII cations and amphipathic, membranepermeable As III anticancer agents under acidic conditions commonly encountered in hypoxic tumor tissues and late endosomes. Computational modeling studies provide clear evidence that the acidtriggered drug-release mechanism for this polymer-caged nanobin (PCN) platform arises from a pH-and temperature-responsive conformation change of the cross-linked polymer cage. As a result, the simultaneous release of both of the active agents in this multicomponent therapeutic enhances the pro-apoptotic activity of AsIII while diminishing its acute toxicity, potentially reducing the undesirable side effects commonly associated with this free drug. The ability to engender acidtriggered release of drugs co-encapsulated inside a liposomal template makes drug delivery using PCN an attractive strategy for triggered drug release.

Original languageEnglish
Pages (from-to)3961-3969
Number of pages9
JournalACS nano
Volume5
Issue number5
DOIs
Publication statusPublished - May 24 2011

Keywords

  • Arsenic trioxide
  • Drug delivery
  • Liposome
  • Molecular modeling
  • Polymer
  • pH-sensitive release

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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