title: Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery.
abstract: The past couple of years have witnessed a tremendous progress in the development of glutathione-responsive nano-vehicles for targeted intracellular drug and gene delivery, as driven by the facts that (i) many therapeutics (e.g. anti-cancer drugs, photosensitizers, and anti-oxidants) and biotherapeutics (e.g. peptide and protein drugs, and siRNA) exert therapeutical effects only inside cells like the cytosol and cell nucleus, and (ii) several intracellular compartments such as cytosol, mitochondria, and cell nucleus contain a high concentration of glutathione (GSH) tripeptides (about 2-10 mM), which is 100 to 1000 times higher than that in the extracellular fluids and circulation (about 2-20 μM). Glutathione has been recognized as an ideal and ubiquitous internal stimulus for rapid destabilization of nano-carriers inside cells to accomplish efficient intracellular drug release. In this paper, we will review recent results on GSH-responsive nano-vehicles in particular micelles, nanoparticles, capsules, polymersomes, nanogels, dendritic and macromolecular drug conjugates, and nano-sized nucleic acid complexes for controlled delivery of anti-cancer drugs (e.g. doxorubicin and paclitaxel), photosensitizers, anti-oxidants, peptides, protein drugs, and nucleic acids (e.g. DNA, siRNA, and antisense oligodeoxynucleotide). The unique disulfide chemistry has enabled novel and versatile designs of multifunctional delivery systems addressing both intracellular and extracellular barriers. We are convinced that GSH-responsive nano-carrier systems have enormous potential in targeted cancer therapy.
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China.
authors.forename: Ru
authors.initials: R
authors.lastname: Cheng
authors.forename: Fang
authors.initials: F
authors.lastname: Feng
authors.forename: Fenghua
authors.initials: F
authors.lastname: Meng
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.forename: Jan
authors.initials: J
authors.lastname: Feijen
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002214:Capsules; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008823:Micelles; D000080385:Nanogels; D053758:Nanoparticles / Q000008:administration & dosage*; D011092:Polyethylene Glycols; D011094:Polyethyleneimine
chemical_list: D002214:Capsules; D008823:Micelles; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D005978:Glutathione