title: Synthesis of cationic polylactides with tunable charge densities as nanocarriers for effective gene delivery.
abstract: Well-defined cationic polylactides (CPLAs) with tertiary amine groups were synthesized by thiol-ene click functionalization of an allyl-functionalized polylactide to yield polymers with tunable charge densities. CPLAs have not previously been utilized in the context of DNA delivery. Thus, plasmid DNA (pDNA) encoding luciferase was delivered to two physiologically distinct cell lines (macrophage and fibroblast) via formation of CPLA/pDNA polyplexes by electrostatic interaction. The formulated polyplexes demonstrated high levels of transfection with low levels of cytotoxicity when compared to a positive control. Biophysical characterization of charge densities at various CPLA/pDNA weight ratios revealed a positive correlation between surface charge and gene delivery. Overall, these results help to elucidate the influence of polyplex charge and size upon the delivery of nucleic acid and support future gene delivery applications using this next-generation biomaterial.
authors: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260-4200, USA.
authors: Charles H
authors: CH
authors: Jones
authors: Chih-Kuang
authors: CK
authors: Chen
authors: Ming
authors: M
authors: Jiang
authors: Lei
authors: L
authors: Fang
authors: Chong
authors: C
authors: Cheng
authors: Blaine A
authors: BA
authors: Pfeifer
mesh_terms: D002412:Cations / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D002412:Cations; D004337:Drug Carriers; D011091:Polyesters; C033616:poly(lactide)