title: Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing charge density for gene delivery.
abstract: Representing a new type of biodegradable cationic block copolymer, well-defined poly(ethylene glycol)-block-cationic polylactides (PEG-b-CPLAs) with tertiary amine-based cationic groups were synthesized by thiol-ene functionalization of an allyl-functionalized diblock precursor. Subsequently the application of PEG-b-CPLAs as biodegradable vectors for the delivery of plasmid DNAs (pDNAs) was investigated. Via the formation of PEG-b-CPLA:pDNA nanocomplexes by spontaneous electrostatic interaction, pDNAs encoding luciferase or enhanced green fluorescent protein were successfully delivered to four physiologically distinct cell lines (including macrophage, fibroblast, epithelial, and stem cell). Formulated nanocomplexes demonstrated high levels of transfection with low levels of cytotoxicity and hemolysis when compared to a positive control. Biophysical characterization of charge densities of nanocomplexes at various polymer:pDNA weight ratios revealed a positive correlation between surface charge and gene delivery. Nanocomplexes with high surface charge densities were utilized in an in vitro serum gene delivery inhibition assay, and effective gene delivery was observed despite high levels of serum. Overall, these results help to elucidate the influence of charge, size, and PEGylation of nanocomplexes upon the delivery of nucleic acids in physiologically relevant conditions.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Amherst, NY 14260, USA.
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Chen
authors.forename: Charles H
authors.initials: CH
authors.lastname: Jones
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Mistriotis
authors.forename: Yun
authors.initials: Y
authors.lastname: Yu
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Ma
authors.forename: Anitha
authors.initials: A
authors.lastname: Ravikrishnan
authors.forename: Ming
authors.initials: M
authors.lastname: Jiang
authors.forename: Stelios T
authors.initials: ST
authors.lastname: Andreadis
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
authors.forename: Chong
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D006801:Humans; D010957:Plasmids / Q000008:administration & dosage*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D002412:Cations; D011091:Polyesters; D011092:Polyethylene Glycols; C033616:poly(lactide); D004247:DNA
keywords: Cationic polymer; Gene delivery; Nanocomplex; PEGylation; Polylactide