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Multifunctional Nanomodulators Regulate Multiple Pathways To Enhance Antitumor Immunity

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journal contribution
posted 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
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.

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