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Guanidinated Thiourea‐Decorated Polyethylenimines for Enhanced Membrane Penetration and Efficient siRNA Delivery
Author(s) -
Li Yuce,
Tian Huayu,
Ding Jianxun,
Lin Lin,
Chen Jie,
Gao Shiqian,
Chen Xuesi
Publication year - 2015
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201500165
Subject(s) - internalization , small interfering rna , rna interference , gene silencing , thiourea , transfection , hela , intracellular , biology , cytotoxicity , luciferase , microbiology and biotechnology , rna , cell , chemistry , biochemistry , gene , in vitro , organic chemistry
RNA interference (RNAi) provides the promising treatments of gene‐related diseases while hindered by the lack of highly efficient delivery platform with low cytotoxicity. Moreover, the intracellular fates of nonviral gene carriers are closely related to their internalization pathway, and eventually influence their RNAi efficiency. Herein, a series of guanidinated thiourea‐modified polyethylenimines (PEI‐MTU‐Gs) are synthesized and utilized as the efficient carriers of small interfering RNA (siRNA) with up to 71.6% inhibition of luciferase activity in the luciferase‐expressing cell lines (i.e., HeLa/Luc cells). The introduction of noncationic hydrogen bond donors, that is, thiourea groups, provides the carriers with much lower cytotoxicities and relatively looser complex structures that facilitate the intracellular release of siRNAs. Furthermore, the multiguanidino structures endow the PEI‐MTU‐G/siRNA complexes with the ability to directly penetrate cell membrane, which facilitates the cellular internalization while avoiding them suffering from the rigorous lysosomes. The results demonstrate PEI‐MTU 35 ‐Gs as promising siRNA carriers for further gene therapy.