Novel polyethyleneimine-R8-heparin nanogel for high-efficiency gene delivery in vitro and in vivo

Drug Delivery

Yan Wang¹  Lan Zhang²  Changyang Gong³  Suleixin Yang³  Ning Wang³  Linjiang Song³  Tao He³  Qinjie Wu³  Xiuqi Liang³ 

[1] Personalized Drug Therapy Key Laboratory of Sichuan Province, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital, Chengdu, P. R. China;Research and Development Department, Guangdong Zhongsheng Pharcacy, Dongguan, Chin;State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P. R. China;

关键词: Nanogel;    polyethyleneimine;    R8;    heparin;    gene delivery;   

DOI  :  10.1080/10717544.2017.1417512

来源: publisher

【 摘 要 】

Gene therapy is an efficient and promising approach to treat malignant tumors. However, protecting the nucleic acid from degradation in vivo and efficient delivering it into tumor cells remain challenges that require to be addressed before gene therapy could be applied in clinic. In this study, we prepared novel polyethyleneimine-RRRRRRRR(R8)-heparin (HPR) nanogel as an efficient gene delivery system, which consists of heparin and cell penetrating peptide R8 grafted low-molecule-weight polyethyleneimine (PEI). Due to the shielding effect of heparin, crosslinking PEI-R8 with heparin was designed to diminish the toxicity of the gene delivery system. Meanwhile, a partial of R8 peptide which located on the surface of HPR nanogel could significantly enhance the cellular uptake. The formed HPR/pDNA complex exhibited effective endolysosomal escape, resulting in a high-efficiency transfection. Furthermore, the HPR could deliver the plasmid which could transcribe human TNF-related apoptosis inducing ligand (phTRAIL), into HCT-116 cells and induce significant cell apoptosis. In addition, HPR/phTRAIL complex showed satisfactory antitumor activity in abdominal metastatic colon carcinoma model. Finally, the antitumor mechanism of HPR/phTRAIL was also explored by western blot and histological analysis. The above results suggested that the HPR nanogel could serve as a promising gene delivery system.

【 授权许可】

CC BY