Kong Hao, Zhao Ruibo, Zhang Quan, Iqbal Muhammed Zubair, Lu Jiaju, Zhao Qingwei, Luo Dandan, Feng Cui, Zhang Kangjian, Liu Xinyuan, Kong Xiangdong
School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Biomater Sci. 2020 Oct 7;8(19):5317-5328. doi: 10.1039/d0bm00681e. Epub 2020 Aug 11.
Oncolytic adenoviruses (OAs) have shown great potential for cancer viral gene therapy in clinical studies. To date, clinical trials have shown that the curative efficacy of OAs is still limited by hepatic sequestration and preexisting neutralizing antibodies (nAbs), which decrease the accumulation of the OAs in tumors. Herein, with the biosilicification method, we encapsulated an OA encoding the anticancer gene Trail (OA-Trail) with silica, which significantly improved virus distribution and tumor inhibition. In vitro and in vivo results indicated that compared with the native OA, biosilicified OA-Trail (OA-Trail@SiO) showed significantly reduced viral clearance in the liver and evaded nAb degradation, inducing an efficacious anticancer effect under the premise of biocompatibility. These achievements present an alternative strategy involving biosilicification for enhanced OA-based cancer gene therapy.
溶瘤腺病毒（OAs）在临床研究中已显示出在癌症病毒基因治疗方面的巨大潜力。迄今为止，临床试验表明，OAs的疗效仍受肝脏滞留和预先存在的中和抗体（nAbs）的限制，这会减少OAs在肿瘤中的积累。在此，我们采用生物矿化方法，用二氧化硅包裹编码抗癌基因Trail的OA（OA-Trail），这显著改善了病毒分布并增强了肿瘤抑制作用。体外和体内结果表明，与天然OA相比，生物矿化的OA-Trail（OA-Trail@SiO）在肝脏中的病毒清除率显著降低，并且能避免被nAb降解，在生物相容性的前提下诱导了有效的抗癌作用。这些成果提出了一种涉及生物矿化的替代策略，以增强基于OA的癌症基因治疗。
