title: Effects of hydrophobic core components in amphiphilic PDMAEMA nanoparticles on siRNA delivery.
abstract: Due to their biodegradable character, polyesters such as polycaprolactone (PCL), poly(D,L-lactide) (PDLLA), and polylactic-co-glycolic acid (PLGA) were widely used as the hydrophobic cores of amphiphilic cationic nanoparticles (NPs) for siRNA delivery. However, fewer researches focused on facilitating siRNA delivery by adjusting the polyester composition of these nanoparticles. Herein, we investigated the contribution of polyester segments in siRNA delivery in vitro by introducing different ratio of DLLA moieties in PCL segments of mPEG-block-PCL-graft-poly(dimethylamino ethyl methacrylate)(PEG-b-PCL-g-PDMAEMA). It was noticed that compared with the other ratios of DLLA moieties, a certain molar ratio (about 70%) of the NPs, named mPEG45-P(CL21-co-DLLA48)-g-(PDMAEMA29)2 (PECLD-70), showed the highest gene knockdown efficiency but poorest cellular uptake ability in vitro. Further research revealed that NPs with various compositions of the polyester cores showed different physicochemical properties including particle size, zeta potential and stiffness, leading to different endocytosis mechanisms thus influencing the cellular uptake efficiency. Subsequently, we observed that the cells treated by PECLD-70 NPs/Cy5 siRNA complexes exhibited more diffuse Cy5 signal distribution than other NPs by confocal laser scanning microscope, which suggested that siRNA delivered by PECLD-70 NPs/Cy5 siRNA complexes possessed of stronger capabilities in escaping from endosome/lysosome, entering the RNA-induced silencing complex (RISC) and cutting the target mRNA efficiently. The different siRNA release profile was dominated by the degradation rate of polyester segments. Therefore, it could be concluded that the adjustment of hydrophobic core of cationic nanoparticles could significantly affect their transfection behavior and appropriate polyester composition should be concerned in designing of analogous siRNA vectors.
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Shangcong
authors.initials: S
authors.lastname: Han
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yidi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Xingwen
authors.initials: X
authors.lastname: Long
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors.forename: Tuo
authors.initials: T
authors.lastname: Wei
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yuanyu
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Shuquan
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
authors.forename: Liandong
authors.initials: L
authors.lastname: Deng
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Cao
authors.affiliation: Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China. Electronic address: liangz@pku.edu.cn.
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China. Electronic address: ajdong@tju.edu.cn.
authors.forename: Anjie
authors.initials: A
authors.lastname: Dong
mesh_terms: D000818:Animals; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009757:Nylons / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*
chemical_list: D008689:Methacrylates; D009757:Nylons; D034741:RNA, Small Interfering; C407037:poly(2-(dimethylamino)ethyl methacrylate)
keywords: Endocytosis mechanism; Nanoparticle; PDMAEMA; Polyester; siRNA delivery