title: Azo-capped polysarcosine-b-polylysine as polypeptide gene vector: A new strategy to improve stability and easy optimization via host-guest interaction.
abstract: Polypeptide has been extensively researched in gene/drug delivery system due to the good biocompatibility. Herein, we synthesized total-polypeptide copolymers, i.e. Azo(azobenzene)-capped polysarcosine-b-polylysine (ASL) with narrow molecular weight distribution by α-amino acid N-carboxyanhydride (NCA) polymerization. Although the molecular weight of PLL segment was only about 6 kDa, ASL could condense DNA effectively and form about 150 nm spherical nanoparticles at N/P ratio of 15. The surface charge was significantly reduced due to the shielding effect of polysarcosine (PSAR) shell. ASL/DNA PeptoPlexes showed good colloidal stability under physiological salt condition and complexation competition stability in the presence of counter polyanion, which might improve the circulation time in vivo. The tip design of azobenzene provided a facile way for ligand modification via host-guest interaction, which could be flexibly optimized by changing its functional tags responding to a request. Our data showed that the introduction of CD-R8 could promote the internalization of gene into cytoplasm and even nucleus owing to the membrane penetrating effect of R8. Cell culture experiments indicated as a total-polypeptide system, ASL showed good cellular viability and comparable gene transfection level as PLL with molecular weight of 50 kDa. Overall, PSAR served as an ideal alternative of PEG and this total-polypeptide system showed us a good direction for gene carrier design.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Du
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Ce
authors.initials: C
authors.lastname: Tian
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ling
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, PR China. Electronic address: yx_wang@zju.edu.cn.
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001391:Azo Compounds / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D003505:Cyclodextrins / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D011107:Polylysine / Q000737:chemistry*; D015203:Reproducibility of Results; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000737:chemistry; D014162:Transfection / Q000379:methods*
chemical_list: D001391:Azo Compounds; D003505:Cyclodextrins; D009842:Oligopeptides; D010455:Peptides; C500307:octa-arginine peptide; D011107:Polylysine; C015475:polysarcosine; D004247:DNA; C009850:azobenzene; D012521:Sarcosine
keywords: Host–guest interaction; PEG alternative; Polypeptide; Polysarcosine