title: Intracellular drug delivery nanocarriers of glutathione-responsive degradable block copolymers having pendant disulfide linkages.
abstract: Self-assembled micelles of amphiphilic block copolymers (ABPs) with stimuli-responsive degradation (SRD) properties have a great promise as nanotherapeutics exhibiting enhanced release of encapsulated therapeutics into targeted cells. Here, thiol-responsive degradable micelles based on a new ABP consisting of a pendant disulfide-labeled methacrylate polymer block (PHMssEt) and a hydrophilic poly(ethylene oxide) (PEO) block were investigated as effective intracellular nanocarriers of anticancer drugs. In response to glutathione (GSH) as a cellular trigger, the cleavage of pendant disulfide linkages in hydrophobic PHMssEt blocks of micellar cores caused the destabilization of self-assembled micelles due to change in hydrophobic/hydrophilic balance. Such GSH-triggered micellar destabilization changed their size distribution with an appearance of large aggregates and led to enhanced release of encapsulated anticancer drugs. Cell culture results from flow cytometry and confocal laser scanning microscopy for cellular uptake as well as cell viability measurements for high anticancer efficacy suggest that new GSH-responsive degradable PEO-b-PHMssEt micelles offer versatility in multifunctional drug delivery applications.
authors: Department of Chemistry and Biochemistry and Center for Nanoscience Research, Concordia University , Montreal, Quebec, Canada H4B 1R6.
authors: Behnoush
authors: B
authors: Khorsand
authors: Gabriel
authors: G
authors: Lapointe
authors: Christopher
authors: C
authors: Brett
authors: Jung Kwon
authors: JK
authors: Oh
mesh_terms: D004220:Disulfides / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers; D005434:Flow Cytometry; D005978:Glutathione / Q000008:administration & dosage* / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D008689:Methacrylates / Q000737:chemistry*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D011092:Polyethylene Glycols / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D008689:Methacrylates; D008823:Micelles; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005978:Glutathione