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. 2021 Jun 2;13(21):24442-24452.
doi: 10.1021/acsami.1c01453. Epub 2021 May 19.

Development of Toll-like Receptor Agonist-Loaded Nanoparticles as Precision Immunotherapy for Reprogramming Tumor-Associated Macrophages

Yun Zhang  1 , Yalan Chen  1 , Jiahao Li  1 , Xueqin Zhu  1 , Yajing Liu  1 , Xiaoxi Wang  1 , Hongfei Wang  1 , Yongjie Yao  1 , Yanfeng Gao  1   2 , Zhenzhen Chen  1
Affiliations

Development of Toll-like Receptor Agonist-Loaded Nanoparticles as Precision Immunotherapy for Reprogramming Tumor-Associated Macrophages

Yun Zhang et al. ACS Appl Mater Interfaces. .

Abstract

Most cancers contain abundant tumor-associated macrophages (TAMs). TAMs usually display a tumor-supportive M2-like phenotype; they promote tumor growth and influence lymphocyte infiltration, leading to immunosuppression. These properties have made TAMs an attractive cancer immunotherapy target. One promising immunotherapeutic strategy involves switching the tumor-promoting immune suppressive microenvironment by reprogramming TAMs. However, clinical trials of M2-like macrophage reprogramming have yielded unsatisfactory results due to their low efficacy and nonselective effects. In this article, we describe the development of M2-like macrophage-targeting nanoparticles (PNP@R@M-T) that efficiently and selectively deliver drugs to 58% of M2-like macrophages, over 39% of M1-like macrophages, and 32% of dendritic cells within 24 h in vivo. Compared with the control groups, administration of PNP@R@M-T dramatically reprogrammed the M2-like macrophages (51%), reduced tumor size (82%), and prolonged survival. Our findings indicate that PNP@R@M-T nanoparticles provide an effective and selective reprogramming strategy for macrophage-mediated cancer immunotherapy.

Keywords: R848; TLR7/8 agonist; precision cancer immunotherapy; tumor immunosuppressive microenvironment (TIME); tumor-associated macrophages reprogramming.

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