Development of Toll-like Receptor Agonist-Loaded Nanoparticles as Precision Immunotherapy for Reprogramming Tumor-Associated Macrophages
| Autor: | Hongfei Wang, Jiahao Li, Xiaoxi Wang, Yongjie Yao, Yun Zhang, Xueqin Zhu, Liu Yajing, Chen Zhenzhen, Yalan Chen, Yanfeng Gao |
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| Rok vydání: | 2021 |
| Předmět: |
Materials science
medicine.medical_treatment 02 engineering and technology Mice 03 medical and health sciences Immune system Cancer immunotherapy In vivo Tumor-Associated Macrophages medicine Animals Humans Macrophage General Materials Science Precision Medicine 030304 developmental biology 0303 health sciences Toll-like receptor Toll-Like Receptors Immunosuppression Immunotherapy 021001 nanoscience & nanotechnology Cancer research Nanoparticles 0210 nano-technology Reprogramming |
| Zdroj: | ACS Applied Materials & Interfaces. 13:24442-24452 |
| ISSN: | 1944-8252 1944-8244 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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