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

نویسندگان

  • Sang-Min Lee
  • One-Sun Lee
  • Thomas V O'Halloran
  • George C Schatz
  • Sonbinh T Nguyen
چکیده

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 Ni(II) cations and amphipathic, membrane-permeable As(III) anticancer agents under acidic conditions commonly encountered in hypoxic tumor tissues and late endosomes. Computational modeling studies provide clear evidence that the acid-triggered 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 As(III) while diminishing its acute toxicity, potentially reducing the undesirable side effects commonly associated with this free drug. The ability to engender acid-triggered release of drugs co-encapsulated inside a liposomal template makes drug delivery using PCN an attractive strategy for triggered drug release.

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عنوان ژورنال:
  • ACS nano

دوره 5 5  شماره 

صفحات  -

تاریخ انتشار 2011