Toxicological Exploration of Peptide-based Cationic Liposomes in siRNA Delivery

Publication date: Available online 25 March 2019Source: Colloids and Surfaces B: BiointerfacesAuthor(s): Yanyan Zhu, Yao Meng, Yinan Zhao, Jie Zhu, Hong Xu, Enxia Zhang, Lei Shi, Linying Du, Guoliang Liu, Chuanmin Zhang, Xiaodong Xu, Xiaohui Kang, Yuhong Zhen, Shubiao ZhangAbstractThe toxicology of cationic liposomes was explored to advance clinical trials of liposome-mediated gene therapy through the analysis of a peptide cationic liposome with DOTAP as a positive control. We first investigated the delivery of luciferase siRNA by several peptide liposomes in mice bearing lung cancer A549 cell xenografts. Of these, a cationic liposome (CDO14) was selected for further investigation. CDO14 efficiently mediated IGF-1R-siRNA delivery and inhibited the growth of the A549 cell xenografts. The in vivo toxicity and toxicological mechanisms of the selected liposome were evaluated to assess its potential utility for gene delivery. Specifically, the effects of CDO14 on mouse body weight, hematology, urine, serum biochemical indices, and histopathology were measured in acute toxicity and subchronic toxicity tests. CDO14 showed limited toxicological effects at low dosages although it induced pulmonary inflammation and liver injury at higher dosages. The toxicity of CDO14 was lower than that of DOTAP, and the toxicity of CDO14 did not change when complexed with siRNA. The pulmonary inflammation induced by CDO14 occurred via expressional up-regulation of the pro-inflammatory cytokines TNF-Î...
Source: Colloids and Surfaces B: Biointerfaces - Category: Biochemistry Source Type: research