title: Controllable Heparin-Based Comb Copolymers and Their Self-assembled Nanoparticles for Gene Delivery.
abstract: Polysaccharide-based copolymers have attracted much attention due to their effective performances. Heparin, as a kind of polysaccharide with high negative charge densities, has attracted much attention in biomedical fields. In this work, we report a flexible way to adjust the solubility of heparin from water to oil via the introduction of tetrabutylammonium groups for further functionalization. A range of heparin-based comb copolymers with poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMEMA), poly(dimethylaminoethyl methacrylate) (PDMAEMA), or PPEGMEMA-b-PDMAEMA side chains were readily synthesized in a MeOH/dimethylsulfoxide mixture via atom-transfer radical polymerization. The heparin-based polymer nanoparticles involving cationic PDMAEMA were produced due to the electrostatic interaction between the negatively charged heparin backbone and PDMAEMA grafts. Then the pDNA condensation ability, cytotoxicity, and gene transfection efficiency of the nanoparticles were characterized in comparison with the reported gene vectors. The nanoparticles were proved to be effective gene vectors with low cytotoxicity and high transfection efficiency. This study demonstrates that by adjusting the solubility of heparin, polymer graft functionalization of heparin can be readily realized for wider applications.
authors.affiliation: Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education , Beijing 100029, China.
authors.forename: Jing-Jun
authors.initials: JJ
authors.lastname: Nie
authors.affiliation: Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education , Beijing 100029, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education , Beijing 100029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education , Beijing 100029, China.
authors.forename: Bingran
authors.initials: B
authors.lastname: Yu
authors.affiliation: Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education , Beijing 100029, China.
authors.forename: Fu-Jian
authors.initials: FJ
authors.lastname: Xu
mesh_terms: D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000009:adverse effects; D006493:Heparin / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008689:Methacrylates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D009757:Nylons / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry; D012995:Solubility; D014162:Transfection / Q000379:methods*
chemical_list: D008689:Methacrylates; D009757:Nylons; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate); C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; D006493:Heparin
keywords: ATRP; functionalization; heparin; nanoparticles; polysaccharide