Multifunctional Nanomodulators Regulate Multiple Pathways To Enhance Antitumor Immunity
journal contributionposted on 08.07.2020, 19:35 by Yadan Zheng, Zhanzhan Zhang, Qi Liu, Yu Zhao, Chunxiong Zheng, Jialei Hao, Kaikai Yi, Ying Wang, Chun Wang, Xinzhi Zhao, Linqi Shi, Chunsheng Kang, Yang Liu
Any type of content formally published in an academic journal, usually following a peer-review process.
Immunosuppression is a key factor leading to a low therapeutic efficiency of the currently used immunotherapies. Monotherapies are unable to overcome immunosuppression because of the complex interplay of immune cells in tumors. Herein, we report a multifunctional nanomodulator (MFNM) as a carrier to deliver different types of immune modulators for comodulating multiple pathways. An MFNM has a core–shell structure, in which small-molecule drugs are encapsulated in a mesoporous silica nanoparticle (MSN) core with a pH-responsive polymer layer. Further, the polymeric shell provides active sites that are readily modifiable by multiple types of antibodies to regulate the immune-related processes. By codelivering cyclophosphamide (CTX), αPD-L1 (B7–H1), and α4-1BB (CD137L) monoclonal antibodies (mAbs) to tumors, an MFNM has been shown to regulate multiple immune pathways and enhance an antitumor immunity. As antibodies and small-molecule drugs loaded in an MFNM can be modified based on the tumor type, the MFNM provides a feasible platform for the development of advanced immunotherapies that require simultaneous modulation of multiple biological processes.