Yan Xiao,Jianqiang Wang,Jun Zhang,Andreas Heise,Meidong Lang
Copolypept(o)ides of polysarcosine (PSar) and poly( N -isopropyl-L-glutamine) (PIGA) with random and block sequence structures were synthesized by ring-opening polymerization (ROP) of sarcosine N -carboxyanhydrides (Sar-NCA) and γ-benzyl- l -glutamate N -carboxyanhydrides (BLG-NCA) and post modification. With different distribution of Sar along the main chain, H-bonding pattern and secondary structure of polypeptides were turned, as well as aggregation and gelation behavior. Both copolypept(o)ides formed hydrogels above their critical gelation concentrations (CGCs) without thermo-sensitivity, which was normally reserved for PEG copolypeptides (eg, PEG- b -PIGA). In particular, a different mechanism from previously reported micellar percolation or fibrillar entanglement was suggested for gelation of the random copolypept(o)ide. Therefore, hydrogels from copolymers of PSar and PIGA represented a new approach to construct easy-handling, biocompatible, biodegradable and thermo-stable gels that could potentially be applied in biomedical fields. Graphical
Jianwei Du,Ce Tian,Yajie Liu,Jun Ling,Youxiang Wang
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.
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