| Affiliation: | 1. Laboratory of Polymer Composites Engineering, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China University of Science and Technology of China, Hefei, Anhui, 230026 China;2. Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033 China;3. Laboratory of Polymer Composites Engineering, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China |
| Abstract: | 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 H2O2 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 H2O2 (<200 μm ) and transport them into the nucleus within 2 h in Hela cells with high safety. Their gene transfection efficiencies were higher than that of PEI25k. The results demonstrated that the hydrogen-bond-induced ultrasensitive esters could be powerfully applied to construct gene delivery systems. |
