细胞内
细胞质
液泡
溶解
癌细胞
生物
癌症研究
调节器
化学
细胞生物学
药物输送
癌症
免疫学
生物化学
基因
有机化学
遗传学
作者
Vishnu Raman,Aleyde Van Eynde,Christopher L. Hall,Victoria E. Wetherby,Samantha A. Whitney,Emily L. Kolewe,Shoshana M. K. Bloom,Abhinav Sharma,Jeanne A. Hardy,Mathieu Bollen,Aleyde Van Eynde,Neil S. Forbes
标识
DOI:10.1038/s41467-021-26367-9
摘要
Abstract Critical cancer pathways often cannot be targeted because of limited efficiency crossing cell membranes. Here we report the development of a Salmonella-based intracellular delivery system to address this challenge. We engineer genetic circuits that (1) activate the regulator flhDC to drive invasion and (2) induce lysis to release proteins into tumor cells. Released protein drugs diffuse from Salmonella containing vacuoles into the cellular cytoplasm where they interact with their therapeutic targets. Control of invasion with flhDC increases delivery over 500 times. The autonomous triggering of lysis after invasion makes the platform self-limiting and prevents drug release in healthy organs. Bacterial delivery of constitutively active caspase-3 blocks the growth of hepatocellular carcinoma and lung metastases, and increases survival in mice. This success in targeted killing of cancer cells provides critical evidence that this approach will be applicable to a wide range of protein drugs for the treatment of solid tumors.
科研通智能强力驱动
Strongly Powered by AbleSci AI