期刊
ADVANCED MATERIALS
卷 33, 期 7, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202003523
关键词
gene silencing; poly(ethylene glycol); serum resistance; siRNA delivery
类别
资金
- National Natural Science Foundation of China [21704061, 81771968]
- Shanghai Sailing Program [17YF1411000]
- Shanghai Municipal Education Commission-Gaofeng Clinical Grant Support [20181705]
- Shanghai Municipal Commission of Health and Family Planning [201840020]
- Shanghai Jiao Tong University [YG2016QN54, ZH2018ZDA05]
A novel PEG modification strategy was proposed in this study, forming PEG/G5PBA/siRNA nanoassemblies through reversible boronate esters, which significantly improved siRNA delivery efficiency under both serum-free and serum-containing conditions.
The transfection efficiency of siRNA mediated by cationic polymers is limited due to the instability of polymers/siRNA complexes in the presence of serum. Poly(ethylene glycol) (PEG) is usually applied to modify cationic polymers, so as to reduce protein and cell adsorption and then to improve siRNA transfection efficiency. However, the polymers' modification with PEG mostly consumes the free amino of the polymers, which can, in turn, reduce the charge density and limit their siRNA transfection efficacy. Here, a new PEG modification strategy that need not consume the surface aminos of polymers is proposed. Catechol-PEG polymers are coated on the surface of phenylboronic acid (PBA)-modified Generation 5 (G5) poly(amidoamine) dendrimers (G5PBA) via reversible boronate esters to establish PEG-modified dendrimer/siRNA nanoassemblies for efficient siRNA delivery. The PEG/G5PBA/siRNA nanoassemblies have positive charge and show excellent gene silencing efficacy in the absence of serum in vitro. More importantly, the PEG/G5PBA/siRNA nanoassemblies also exhibit excellent serum resistance and gene silencing efficacy in serum-containing medium. Furthermore, the effective antiserum and gene silencing efficacy elicited by these nanoassemblies lead to excellent antitumor effects in vivo. This proposed strategy constitutes an important approach to reach an excellent gene silencing efficacy in the presence of serum.
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