Stark Marie, Cheng R Holland
Department of Molecular and Cellular Biology, University of California, Davis, CA, USA.
Pharm Pat Anal. 2016 Sep;5(5):307-17. doi: 10.4155/ppa-2016-0021.
Nanoparticle diagnostics and therapeutics (nanotheranostics) have significantly advanced cancer detection and treatment. However, many nanotheranostics are ineffective due to defects in tumor localization and bioavailability. An engineered Hepatitis E Virus (HEV) nanocapsid is a proposed platform for targeted cancer-cell delivery. Self-assembling from HEV capsid subunits, nanocapsids retain the capacity to enter cells and resist proteolytic/acidic conditions, but lack infectious viral elements. The nanocapsid surface was modified for chemical activation to confer tumor-specific targeting and detection, immune-response manipulation and controlled theranostic delivery. Nanotheranostic molecules can be packaged in the hollow nanocapsid shell during in vitro assembly. Complementing the adapted stability and cell-entry characteristics of the HEV capsid, a modified nanocapsid serves as a tunable tumor-targeting platform for nanotheronostic delivery.
纳米颗粒诊断与治疗(纳米诊疗)在癌症检测和治疗方面取得了显著进展。然而,由于肿瘤定位和生物利用度方面的缺陷,许多纳米诊疗方法效果不佳。一种经过工程改造的戊型肝炎病毒(HEV)纳米衣壳被提议作为靶向癌细胞递送的平台。纳米衣壳由HEV衣壳亚基自组装而成,保留了进入细胞和抵抗蛋白水解/酸性条件的能力,但缺乏感染性病毒元件。对纳米衣壳表面进行化学活化修饰,以赋予肿瘤特异性靶向和检测、免疫反应调控以及可控的诊疗递送能力。纳米诊疗分子可在体外组装过程中包装在中空的纳米衣壳壳内。结合HEV衣壳适应的稳定性和细胞进入特性,经过修饰的纳米衣壳可作为用于纳米诊疗递送的可调谐肿瘤靶向平台。