Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy

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• 作者：Jianhua Chen ; Pei Gao ; Sujing Yuan ; Rongxin Li ; Aimin Ni ; Liang Chu ; Li Ding ; Ying Sun ; Xin-Yuan Liu ; Yourong Duan
• 刊名：ACS Nano
• 出版年：2016
• 出版时间：December 27, 2016
• 年：2016
• 卷：10
• 期：12
• 页码：11548-11560
• 全文大小：886K
• ISSN：1936-086X

文摘

Oncolytic adenovirus (Onco^Ad) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of Onco^Ad is hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-Onco^Ad (PLC-Onco^Ad) 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 Onco^Ad protected it from neutralization by pre-existing neutralizing antibody. PLC-Onco^Ad 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-Onco^Ad delivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.