溶瘤腺病毒
溶瘤病毒
全身给药
体内
免疫系统
遗传增强
药理学
毒性
癌症研究
基因传递
癌症
病毒载体
医学
生物
免疫学
基因
生物化学
内科学
生物技术
重组DNA
作者
Jianhua Chen,Pei Gao,Sujing Yuan,Rongxin Li,Ai-Min Ni,Liang Chu,Li Ding,Ying Sun,Xinyuan Liu,Yourong Duan
出处
期刊:ACS Nano
[American Chemical Society]
日期:2016-12-15
卷期号:10 (12): 11548-11560
被引量:82
标识
DOI:10.1021/acsnano.6b06182
摘要
Oncolytic adenovirus (OncoAd) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of OncoAd is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-OncoAd (PLC-OncoAd) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response. In addition, masking the surface of OncoAd protected it from neutralization by pre-existing neutralizing antibody. PLC-OncoAd achieved efficient targeted delivery in Huh-7-bearing nude mice, and intravenous administration of a high dose of PLC-ZD55-IL-24 increased therapeutic efficacy without inducing toxicity. The developed PLC-OncoAd delivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.
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