title: Triggered release of pharmacophores from [Ni(HAsO₃)]-loaded polymer-caged nanobin enhances pro-apoptotic activity: a combined experimental and theoretical study.
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 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.
authors.affiliation: Department of Chemistry and Center of Cancer Nanotechnology Excellence, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: One-Sun
authors.initials: OS
authors.lastname: Lee
authors.forename: Thomas V
authors.initials: TV
authors.lastname: O'Halloran
authors.forename: George C
authors.initials: GC
authors.lastname: Schatz
authors.forename: Sonbinh T
authors.initials: ST
authors.lastname: Nguyen
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004357:Drug Synergism; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008422:Materials Testing; D008956:Models, Chemical; D053769:Nanocapsules / Q000737:chemistry*; D009532:Nickel / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011108:Polymers; D009532:Nickel