Guanidyl and imidazolyl integration group-modified PAMAM for gastric adenocarcinoma gene therapy.

摘要: Background Gene therapy has become a potential strategy for cancer treatment. However, the development of efficient gene vectors restricts application Functionalization polymers with functional groups can significantly improve their transfection efficacy. Methods Guanidyl form bidentate hydrogen phosphate and are present in DNA cell membranes, thus increasing condensation cellular uptake. Imidazolyl high buffering capacity endosomal/lysosomal acidic environment, facilitating endosome/lysosome escape. We designed structure-integrated group guanidyl imidazolyl, 2-aminoimidazole (AM), which was conjugated to PAMAM generation 2 (G2) gastric adenocarcinoma. Results Molecular docking results illustrated that G2-AM bound molecule effectively via multiple interactions. A quantitative luciferase assay showed efficacy G2-AM/pGL3 approximately 100-fold greater than G2/pGL3, 90-fold imidazolyl-modified G2 (G2-M) /pGL3 G5/pGL3 without additional cytotoxicity. After introducing pTRAIL into adenocarcinoma cells, apoptosis ratio cells treated G2-AM/pTRAIL 36.95%, is much larger corresponding G2/pTRAIL (7.45%), G2-M/pTRAIL (11.33%) G5/pTRAIL (23.2%). In xenograft model, vivo G2-AM/pRFP G2/pRFP G2-M/pRFP. Conclusions These demonstrate AM could be modified cationic delivery therapy.