Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes

doi:10.7150/thno.50928

	Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes
	Han, Shulan 1,2; Wang, Wenjie 2; Wang, Shengfang 2; Yang, Tingyuan 1; Zhang, Guifeng 1; Wang, Di 3; Ju, Ruijun 3; Lu, Yu 4; Wang, Huimei 2; Wang, Lianyan 1
刊名	THERANOSTICS
	2021
卷号	11 期号:6 页码:2892-2916
关键词	nano-complex tumor associated macrophage tumor microenvironment anti-tumor therapy
ISSN号	1838-7640
DOI	10.7150/thno.50928
英文摘要	Background: Among the many immunosuppressive cells in the tumor microenvironment, tumor-associated-macrophages (TAMs) are well known to contribute to tumor development. TAMs can be conditioned (polarized) to transition between classical M1-like macrophages, or alternatively to M2-like macrophages. Both are regulated by signaling molecules in the microenvironment. M1-like TAMs can secrete classic inflammatory cytokines that kill tumors by promoting tumor cell necrosis and immune cell infiltration into the tumor microenvironment. In contrast, M2-like TAMs exhibit powerful tumor-promoting functions, including degradation of tumor extracellular matrix, destruction of basement membrane, promotion of angiogenesis, and recruitment of immunosuppressor cells, all of which further promote tumor progression and distal metastasis. Therefore, remodeling the tumor microenvironment by reversing the TAM phenotype will be favorable for tumor therapy, especially immunotherapy. Methods: PLGA nanoparticles encapsulating baicalin and melanoma antigen Hgp peptide fragment 25-33 were fabricated using the ultrasonic double-emulsion technique. The nanoparticles were further loaded with CpG fragments and used conjugated M2pep and a-pep peptides on their surfaces to produce novel nano-complexes. The capability to target M2-like TAMs and anti-tumor immunotherapy effects of nano-complexes were evaluated by flow cytometry and confocal microscopy in vitro. We also investigated the survival and histopathology of murine melanoma models administrated with different nanocomplexes. Improvements in the tumor microenvironment for immune attack of melanoma-bearing mice were also assessed. Results: The nano-complexes were effectively ingested by M2-like TAMs in vitro and in vivo, and the acidic lysosomal environment triggered the disintegration of polydopamine from the nanoparticle surface, which resulted in the release of the payloads. The released CpG played an important role in transforming the M2-like TAMs into the M1-like phenotype that further secreted inflammatory cytokines. The reversal of TAM released cytokines and gradually suppressed tumor angiogenesis, permitting the remodeling of the tumor microenvironment. Moreover, the activated TAMs also presented antigen to T cells, which further stimulated the antitumor immune response that inhibited tumor metastasis. Activated T cells released cytokines, which stimulated NK cell infiltration and directly resulted in killing tumor cells. The baicalin released by M1-like TAMs also killed tumor cells. Conclusion: The nano-complexes facilitated baicalin, antigen, and immunostimulant delivery to M2-like TAMs, which polarized and reversed the M2-like TAM phenotype and remodeled the tumor microenvironment to allow killing of tumor cells.
资助项目	National Science and Technology Major Project of China[2016ZX10004001-005] ; National Science Foundation of China[81973262] ; Fundamental Research Funds for the Central Universities[2572017EA03] ; Fundamental Research Funds for the Central Universities[2572018AA22]
WOS关键词	CANCER STATISTICS ; POLARIZATION ; BAICALIN ; CELLS ; NANOPARTICLES ; RESPONSES ; DELIVERY ; CARCINOMA ; APOPTOSIS ; MIGRATION
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	IVYSPRING INT PUBL
WOS记录号	WOS:000604981700025
资助机构	National Science and Technology Major Project of China ; National Science Foundation of China ; Fundamental Research Funds for the Central Universities
内容类型	期刊论文
源URL	[http://ir.ipe.ac.cn/handle/122111/43053]
专题	中国科学院过程工程研究所
通讯作者	Wang, Huimei; Wang, Lianyan
作者单位	1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Key Lab Green Proc & Engn, Beijing 100190, Peoples R China 2.Northeast Forestry Univ, Coll Chem Chem Engn & Resource Utilizat, Harbin 150040, Peoples R China 3.Beijing Inst Petrochem Technol, Beijing 102617, Peoples R China 4.Jiangsu Acad Agr Sci, Inst Vet Immunol & Engn, Nanjing 210014, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Han, Shulan,Wang, Wenjie,Wang, Shengfang,et al. Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes[J]. THERANOSTICS,2021,11(6):2892-2916.
APA	Han, Shulan.,Wang, Wenjie.,Wang, Shengfang.,Yang, Tingyuan.,Zhang, Guifeng.,...&Wang, Lianyan.(2021).Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes.THERANOSTICS,11(6),2892-2916.
MLA	Han, Shulan,et al."Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes".THERANOSTICS 11.6(2021):2892-2916.