DGIST Scholar: Thiol-responsive gemini poly(ethylene glycol)-poly(lactide) with a cystine disulfide spacer as an intracellular drug delivery nanocarrier

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Thiol-responsive gemini poly(ethylene glycol)-poly(lactide) with a cystine disulfide spacer as an intracellular drug delivery nanocarrier

Title: Thiol-responsive gemini poly(ethylene glycol)-poly(lactide) with a cystine disulfide spacer as an intracellular drug delivery nanocarrier

Author(s): Kim, Hyun-Chul ; Kim, Eunjoo ; Ha, Tae-Lin ; Jeong, Sang Won ; Lee, Se Guen ; Lee, Sung Jun ; Lee, Boram

DGIST Authors: Kim, Hyun-Chul ; Kim, Eunjoo ; Jeong, Sang Won ; Lee, Se Guen ; Lee, Sung Jun

Subject: Antineoplastic Activity ; Biodegradability ; Biodegradable ; Biodegradable Polymers ; Cell Culture ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Cell Transport ; Cell Viability ; Chemistry ; Chromatography, Gel ; Confocal Laser Microscopy ; Controlled Drug Delivery ; Controlled Study ; Cystine ; Cystines ; Cytotoxicity ; Disulfide ; Disulfide-Thiol Exchange ; Disulfide-Thiol Exchanges ; Disulfides ; Doxorubicin ; Drug Carrier ; Drug Carriers ; Drug Delivery ; Drug Delivery System ; Drug Delivery Systems ; Drug Effects ; Drug Efficacy ; Enzyme Inhibition ; Gel Permeation Chromatography ; Gemini Surfactant ; Gemini Surfactants ; Glutathione ; Human ; Human Cell ; Humans ; Hydrophilicity ; Hydrophobicity ; Light Scattering ; Macrogol ; Macrogol Derivative ; Micelle ; Micelles ; Micellization ; Nano-Carrier ; Nanoparticle ; Nanoparticles ; Particle Size ; Poly(Ethyleneglycol-Lactide) ; Polyester ; Polyesters ; Polyethylene Glycols ; Polylactide ; Polymerization ; Polymers ; Polyols ; Size Exclusion Chromatography ; Stimulus-Sensitive Polymers ; Sulfhydryl Compounds ; Sulfur Compounds ; Synthesis ; Thiol Derivative ; Tumor Cell Line ; Ultrastructure

Abstract: Thiol-responsive gemini micelles consisting of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic polylactide (PLA) blocks with a cystine disulfide spacer were reported as effective intracellular nanocarriers of drugs. In the presence of cellular glutathione (GSH) as a reducing agent, gemini micelles gradually destabilize into monomeric micelles through cleavage of the cystine linkage. This destabilization of the gemini micelles changed their size distribution, with the appearance of small aggregates, and led to the enhanced release of encapsulated doxorubicin (DOX). The results obtained from cell culture via confocal laser scanning microscopy (CLSM) for cellular uptake, as well as cell viability measurements for anticancer efficacy suggest the potential of disulfide-based gemini polymeric micelles as controlled drug delivery carriers. © 2015 Elsevier B.V.