Guanidyl and imidazolyl integration group-modified PAMAM for gastric adenocarcinoma gene therapy
Guanidyl and imidazolyl integration group-modified PAMAM for gastric adenocarcinoma gene therapy
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DOI：
10.1002/jgm.3240
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Min Liu
中科院分区：
文献类型：
--
作者：
Dongli Wang;Jing Wang;Jie Song;Qing Shen;Ruifeng Wang;Weiyue Lu;Jun Pan;Cao Xie;Min Liu
Background: Gene therapy has become a potential strategy for cancer treatment..However, the development of efficient gene vectors restricts the application for cancer.gene treatment. Functionalization of polymers with functional groups can significantly.improve their transfection efficacy..Methods: Guanidyl can form bidentate hydrogen with the phosphate groups and.phosphate groups are present in DNA and cell membranes, thus increasing DNA.condensation and cellular uptake. Imidazolyl has high buffering capacity in endosomal/.lysosomal acidic environment, facilitating endosome/lysosome escape. We designed a.structure-integrated group of guanidyl and imidazolyl, 2-aminoimidazole (AM), which was.conjugated to PAMAM generation 2 (G2) for gene therapy of gastric adenocarcinoma..Results: Molecular docking results illustrated that G2-AM bound with DNA molecule.effectively via multiple interactions. A quantitative luciferase assay showed that.the transfection efficacy of G2-AM/pGL3 was approximately 100-fold greater than.that of G2/pGL3, 90-fold greater than that of imidazolyl-modified G2 (G2-M) /pGL3.and 100-fold greater than that of G5/pGL3 without additional cytotoxicity. After.introducing the pTRAIL gene into gastric adenocarcinoma cells, the apoptosis ratio.of gastric adenocarcinoma cells treated with G2-AM/pTRAIL was 36.95%, which is.much larger than the corresponding ratio of G2/pTRAIL (7.45%), G2-M/pTRAIL.(11.33%) and G5/pTRAIL (23.2%). In a gastric adenocarcinoma xenograft model,.the in vivo transfection efficacy of G2-AM/pRFP was much greater than that of.G2/pRFP and G2-M/pRFP..Conclusions: These results demonstrate that AM could be modified with cationic polymers for potential .application in gene delivery and gastric adenocarcinoma gene therapy.
