pIL-12 delivered by polymer based nanovector for anti-tumor genetherapy  

作　　者：Lianbin Wen Xin Zan Qidi Pang Yuzhu Hu Songping Zheng Mengni Ran Xiang Gao Xiang Wang Bilan Wang 

机构地区：[1]Department of Geriatrics,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Chengdu 610072,China [2]Department of Neurosurgery,West China Hospital,Sichuan University,Chengdu 610041,China [3]Department of Infection Management,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China [4]Department of Radiation Oncology,Cancer Center,West China Hospital,West China Medical School,Sichuan University,Chengdu 610041,China [5]Department of Pharmacy,West China Second University Hospital of Sichuan University,Chengdu 610041,China [6]Pharmaceutical Department,Chongqing University Three Gorges Hospital,Chongqing 404000,China

出　　处：《Chinese Chemical Letters》2023年第11期209-213,共5页中国化学快报（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.81972347);the Key R&D Projects of the Science and Technology Department of Sichuan Province(No.2022YFS0324).

摘　　要：Finding more effective and safe non-viral vectors to transfer genes into cancer cells has become the key of immune gene therapy for cancer.Herein a triblock compound MPEG_(2000)-PDLLA_(4000)-MPEG_(2000) modified by cationic liposome DOTAP was used as a non-viral vector DOTAP/MPEG_(2000)-PDLLA_(4000)-MPEG_(2000)(DMPM)to effectively transfer interleukin(IL)-12 plasmid(pIL-12)into tumor tissue.IL-12 produced by transfected tumor cells successfully inducing lymphocyte proliferation and promoting interferon-γ(IFN-γ)secretion,which resulted in tumor cells death.The ability of DMPM to transfer pIL-12 and the immune effect induced by IL-12 in cells had been explored.The anti-tumor effect,mechanism and safety of pIL-12/DMPM in mice cancer model were investigated in this study.Our results showed that the pIL-12 transferred by DMPM was highly expressed both in CT26 cells and B16-F10 cells.IL-12 expressed in the culture supernatant of transfected tumor cells stimulated lymphocyte proliferation and promoted IFN-γsecretion.The experimental result confirmed that pIL-12/DMPM therapy significantly reduced tumor growth in mice model.We designed the nanocomposite DMPM to deliver pIL-12 for cancer treatment and explored its therapeutic efficacy and the underlying anti-tumor mechanism.Our study suggested pIL-12 loaded by DMPM complex would be an effective strategy for cancer treatment.

关 键 词：Non-viral vector Cancer gene therapy pIL-12 Immune response NANOCOMPOSITE 

分 类 号：R73[医药卫生—肿瘤]