title: Biodegradable copolymers with identical cationic segments and their performance in siRNA delivery.
abstract: The biodegradable cationic copolymers monomethoxy poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(L-lysine) (mPEG-b-PCL-b-PLL, further abbr. as "M") with a PCL block of different lengths and with a triazole linkage between the PCL and PLL blocks were synthesized via ring-opening polymerization of ε-caprolactone and L-lysine N-carboxyanhydride and click reactions. With the copolymer without the PCL block (mPEG-b-PLL, further abbr. as "P") as a control, self-assembling and complexation of these copolymers with siRNA were studied. siRNA-loading capacity, siRNA delivery performance and cellular uptake of the complexation products, namely complex from P (P-complex) and complexes from M1 and M2 (M1-complex and M2-complex), were further examined and correlated to their block-copolymer compositions. The results showed the block copolymers P, M1 and M2 have strong enough binding ability so that the complexes formed can resist the heparin displacement and RNase degradation. Compared to P-complex, M-complexes have smaller size and higher particle density so that they can be internalized via endocytosis more easily than free siRNA or P-complex and they display higher siRNA delivery efficiency and higher gene silencing efficiency than P-complex. The silencing efficiency of micellar complex is close to that of Lipofectamine(TM) 2000 and much better than PEI-25kDa. Therefore, mPEG-b-PCL-b-PLL is expected to be a promising siRNA carrier.
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Ruogu
authors.initials: R
authors.lastname: Qi
authors.forename: Shi
authors.initials: S
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Haihua
authors.initials: H
authors.lastname: Xiao
authors.forename: Lesan
authors.initials: L
authors.lastname: Yan
authors.forename: Yubin
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D002412:Cations; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D057930:Click Chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D024202:Electrophoretic Mobility Shift Assay; D004705:Endocytosis; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011107:Polylysine / Q000138:chemical synthesis / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D004337:Drug Carriers; D011091:Polyesters; D034741:RNA, Small Interfering; C572240:methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone)-b-poly(L-lysine); D011107:Polylysine