title: Reductively-sheddable cationic nanocarriers for dual chemotherapy and gene therapy with enhanced release.
abstract: The development of a versatile strategy to synthesize cationic nanocarriers capable of co-delivery and enhanced release of drugs and oligonucleotides is promising for synergic dual chemotherapy and gene therapy. Herein, we report a novel cationic amphiphilic diblock copolymer having a single reduction-responsive disulfide linkage at a junction between a FDA-approved polylactide (PLA) block and a cationic methacrylate block (C-ssABP). The amphiphilic design of the C-ssABP enables the formation of cationic micellar aggregates possessing hydrophobic PLA cores, encapsulating anticancer drugs; cationic coronas, ensuring complementary complexation with negatively-charged oligonucleotides through electrostatic interactions; and disulfides at interfaces, leading to enhanced release of both encapsulated drugs and complexed oligonucleotides. The reduction-responsive intracellular trafficking results from flow cytometry, confocal laser scanning microscopy, and cell viability, as well as in vitro gene transfection assay suggest that C-ssABP offers versatility as an effective nanocarrier platform for dual chemotherapy and gene therapy.
authors.affiliation: Department of Chemistry and Biochemistry, Centre for NanoScience Research, Concordia University, Montreal, Quebec, Canada H4B 1R6.
authors.forename: Na Re
authors.initials: NR
authors.lastname: Ko
authors.affiliation: Department of Chemistry and Biochemistry, Centre for NanoScience Research, Concordia University, Montreal, Quebec, Canada H4B 1R6.
authors.forename: Jack
authors.initials: J
authors.lastname: Cheong
authors.affiliation: Department of Chemistry and Biochemistry, Centre for NanoScience Research, Concordia University, Montreal, Quebec, Canada H4B 1R6.
authors.forename: Anne
authors.initials: A
authors.lastname: Noronha
authors.affiliation: Department of Chemistry and Biochemistry, Centre for NanoScience Research, Concordia University, Montreal, Quebec, Canada H4B 1R6. Electronic address: Chris.Wilds@concordia.ca.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wilds
authors.affiliation: Department of Chemistry and Biochemistry, Centre for NanoScience Research, Concordia University, Montreal, Quebec, Canada H4B 1R6. Electronic address: john.oh@concordia.ca.
authors.forename: Jung Kwon
authors.initials: JK
authors.lastname: Oh
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry*; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D015316:Genetic Therapy; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates / Q000737:chemistry; D015394:Molecular Structure; D049329:Nanostructures / Q000737:chemistry*; D010084:Oxidation-Reduction; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D013499:Surface Properties; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D002412:Cations; D004337:Drug Carriers; D008689:Methacrylates; D011091:Polyesters; D013501:Surface-Active Agents; C033616:poly(lactide)
keywords: Block copolymer; Co-delivery; Drug delivery; Enhanced release; Oligonucleotide delivery; Reduction-responsive degradation