| Title | Structural exploration of hydrophobic core in polycationic micelles for improving siRNA delivery efficiency and cell viability |
| Authors | Huang, Wenjun Wang, Xiaoxia Wang, Changrong Du, Lili Zhang, Jianhua Deng, Liandong Cao, Huiqing Dong, Anjie |
| Affiliation | Tianjin Univ, Key Lab Syst Bioengn, Dept Polymer Sci & Technol, Sch Chem Engn & Technol,Minist Educ, Tianjin 300072, Peoples R China Collaborat Innovat Ctr Chem Sci & Engn Tianjin, Tianjin 300072, Peoples R China Peking Univ, Inst Mol Med, Lab Nucle Acid Technol, Beijing 100871, Peoples R China |
| Issue Date | 2019 |
| Publisher | JOURNAL OF MATERIALS CHEMISTRY B |
| Abstract | Improving siRNA delivery efficiency often encounters a dilemma with poor or decreased biocompatibility for polycationic micelles. To address this dilemma, this work focused on a structural exploration of the hydrophobic core in amphiphilic polycationic micelles by preparing two amphiphilic polycations with block or random hydrophobic segments, poly(ethylene glycol)-block-poly(aminoethyl methacrylate)-block-poly(2-diamylamine ethyl methacrylate)-block-poly(2-diethylamine ethyl methacrylate) (mPEG-PAMA-PD5A-PDEA, PADE) and poly(ethylene glycol)-block-poly(aminoethyl methacrylate)-block-poly(2-diamylamine ethyl methacrylate-co-2-diethylamine ethyl methacrylate) (mPEG-PAMA-P(D5A/DEA), PA(D/E)). The properties of the two copolymers and their self-assembly micelles were characterized, including structure, morphology, size and zeta potential. Cytotoxicity, siRNA silencing efficiency and cellular uptake of PADE/siRNA and PA(D/E)/siRNA complexes were evaluated in HepG2 and MDA-MB-231 cells in vitro. The endosome escape and intracellular distribution of PADE/siRNA and PA(D/E)/siRNA in HepG2 cells were also observed by CLSM. Significantly, the results indicated that PA(D/E)/siRNA showed not only better gene silencing efficiency but also lower cytotoxicity, which may be attributed to the homogeneous morphology of the hydrophobic core of PA(D/E) micelles. Therefore, this work provides a new pathway to overcome the dilemma between siRNA delivery efficiency and biocompatibility for the development of efficient polycation carriers. |
| URI | http://hdl.handle.net/20.500.11897/550675 |
| ISSN | 2050-750X |
| DOI | 10.1039/c8tb02706d |
| Indexed | SCI(E) EI |
| Appears in Collections: | 分子医学研究所 |
