title: Enzymatic PEGylated Poly(lactone-co-β-amino ester) Nanoparticles as Biodegradable, Biocompatible and Stable Vectors for Gene Delivery.
abstract: We have developed new, efficient gene delivery systems based on PEGylated poly(lactone-co-β-amino ester) block copolymers that are biodegradable, stable and low in toxicity. The PEG-poly[PDL-co-3-(4-(methylene)piperidin-1-yl)propanoate] (PEG-PPM) diblock and PPM-PEG-PPM triblock copolymers with various compositions were synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL) and ethyl 3-(4-(hydroxymethyl)piperidin-1-yl)propanoate (EHMPP) with an appropriate PEG (MeO-PEG-OH or HO-PEG-OH). The amphiphilic block copolymers are capable of condensing DNA in aqueous medium via a self-assembly process to form polyplex micelle nanoparticles with desirable particle sizes (70-140 nm). These micelles possess low CMC values and are stable in the medium containing serum protein molecules (FBS). Among the PEG-PPM and PPM-PEG-PPM micelles, the PEG-PPM-15% PDL micelle particles exhibited high DNA-binding ability, the fastest cellular uptake rate and highest gene transfection efficacy. Flow cytometry analysis shows that LucDNA/PEG-PPM-15% PDL polyplex micelles can effectively escape from endosomal degradation after cellular uptake likely due to the presence of the tertiary amine groups in the copolymer chains that act as proton sponges. In vitro cytotoxicity and hemolysis assay experiments indicate that all copolymer samples are nonhemolytic and have minimal toxicity toward COS-7 cells within the polymer concentration range (≤200 μg/mL) used for the gene transfection. These results demonstrate that the PEGylated poly(lactone-co-β-amino ester) block copolymers are promising new vectors for gene delivery applications.
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Yingqin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Jinbiao
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University , Guangzhou, Guangdong 510006, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Biomedical Engineering, Molecular Innovations Center, Yale University , 600 West Campus Drive, West Haven, Connecticut 06516, United States.
authors.forename: Zhaozhong
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D005434:Flow Cytometry; D005453:Fluorescence; D018014:Gene Transfer Techniques; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008049:Lipase; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D004952:Esters; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C000611686:poly(ethylene glycol)-block-poly(omega-pentadecalactone-co-3-(4-(methylene)piperidin-1-yl)propanoate); D011092:Polyethylene Glycols; D004247:DNA; D008049:Lipase
keywords: PEGylation; biodegradable; block copolymer; gene delivery; lipase; micelle; nanoparticle; poly(lactone-co-β-amino ester)