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Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy
ACS Nano ( IF 15.8 ) Pub Date : 2016-12-15 00:00:00 , DOI: 10.1021/acsnano.6b06182 Jianhua Chen 1 , Pei Gao 1 , Sujing Yuan 2 , Rongxin Li 1 , Aimin Ni 2 , Liang Chu 2 , Li Ding 1 , Ying Sun 1 , Xin-Yuan Liu 2 , Yourong Duan 1
ACS Nano ( IF 15.8 ) Pub Date : 2016-12-15 00:00:00 , DOI: 10.1021/acsnano.6b06182 Jianhua Chen 1 , Pei Gao 1 , Sujing Yuan 2 , Rongxin Li 1 , Aimin Ni 2 , Liang Chu 2 , Li Ding 1 , Ying Sun 1 , Xin-Yuan Liu 2 , Yourong Duan 1
Affiliation
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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.
中文翻译：
脂质和磷酸钙包被的溶瘤腺病毒复合物用于癌症基因治疗
溶瘤腺病毒（Onco Ad）是治疗癌症的有前途的治疗剂。然而，体内的肝隔离和宿主免疫应答阻碍了Onco Ad的治疗潜力。在这里，我们为携带IL-24基因的溶瘤腺病毒ZD55-IL-24构建了PEG /脂质/磷酸钙（CaP）-Onco Ad（PLC-Onco Ad）递送系统。带负电荷的PLC-ZD55-IL-24分散并抵抗血清诱导的聚集。与裸ZD55-IL-24相比，PLC-ZD55-IL-24在BALB / c小鼠中的全身给药可减少肝脏的螯合和全身毒性，并逃避先天免疫反应。此外，遮盖Onco Ad的表面通过预先存在的中和抗体保护它免受中和。PLC-Onco Ad在带有Huh-7的裸鼠中实现了有效的靶向递送，静脉内给予高剂量的PLC-ZD55-IL-24可提高治疗效果，而不会引起毒性。开发的PLC-Onco Ad投放系统代表了基于溶瘤腺病毒的体内癌症基因治疗的有希望的改进。
更新日期：2016-12-15
中文翻译：
脂质和磷酸钙包被的溶瘤腺病毒复合物用于癌症基因治疗
溶瘤腺病毒（Onco Ad）是治疗癌症的有前途的治疗剂。然而，体内的肝隔离和宿主免疫应答阻碍了Onco Ad的治疗潜力。在这里，我们为携带IL-24基因的溶瘤腺病毒ZD55-IL-24构建了PEG /脂质/磷酸钙（CaP）-Onco Ad（PLC-Onco Ad）递送系统。带负电荷的PLC-ZD55-IL-24分散并抵抗血清诱导的聚集。与裸ZD55-IL-24相比，PLC-ZD55-IL-24在BALB / c小鼠中的全身给药可减少肝脏的螯合和全身毒性，并逃避先天免疫反应。此外，遮盖Onco Ad的表面通过预先存在的中和抗体保护它免受中和。PLC-Onco Ad在带有Huh-7的裸鼠中实现了有效的靶向递送，静脉内给予高剂量的PLC-ZD55-IL-24可提高治疗效果，而不会引起毒性。开发的PLC-Onco Ad投放系统代表了基于溶瘤腺病毒的体内癌症基因治疗的有希望的改进。
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