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Hydrogen‐Bond Cyclization Programming of Ultrasensitive Esters and Its Application in Gene Delivery
Author(s) -
Li Shengran,
Yan Xinxin,
Qu Yangchun,
Wang Wenliang,
Chen Binggang,
Ma Xiaojing,
Liu Sanrong,
Yu Xifei
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201901173
Subject(s) - chemistry , hydrogen bond , gene delivery , hydrolysis , dendrimer , molecule , linker , amine gas treating , combinatorial chemistry , cleave , polymer chemistry , transfection , organic chemistry , gene , enzyme , biochemistry , computer science , operating system
The ester bond as a universal linker has recently been applied in gene delivery systems owing to its efficient gene release by electrostatic repulsion after its cleavage. However, the ester bond is nonlabile and is difficult to cleave in cells. This work reports a method in which a secondary amine was introduced to the β‐position of the ester bond to generate a hydrogen‐bond cyclization (HBC) structure that can make the ester bond hydrolysis ultrafast. A series of molecules comprising ultrasensitive esters that can be activated by H 2 O 2 were synthesized, and it was found that those able to form an HBC structure showed complete ester hydrolysis within 5 h in both water and phosphate‐buffered saline solution, which was several times faster than other methods reported. Then, a series of amphiphilic poly(amidoamine) dendrimers were constructed, comprising the ultrasensitive ester groups for gene delivery; it was found that they could effectively release genes under quite a low concentration of H 2 O 2 (<200 μ m ) and transport them into the nucleus within 2 h in Hela cells with high safety. Their gene transfection efficiencies were higher than that of PEI 25k . The results demonstrated that the hydrogen‐bond‐induced ultrasensitive esters could be powerfully applied to construct gene delivery systems.