title: Polymeric nanoparticles promote macrophage reversal from M2 to M1 phenotypes in the tumor microenvironment.
abstract: Immunotherapy has shown promising treatment effects for a variety of cancers. However, the immune treatment efficiency for solid tumors is limited owing to insufficient infiltration of immune cells into solid tumors. The conversion of tumor-supportive macrophages to tumor-suppressive macrophages, inducing the functional reversal of macrophages, is an effective method and contributes to a subsequent antitumor response. The current challenge in the field is the poor distribution and systemic side effects associated with the use of cytokines. As a solution to this issue, we designed and synthesized microenvironment-responsive nanoparticles (P) with IL-12 payload (IL-12⊂P1). These nanoparticles could promote the systemic administration and release of IL-12 in the tumor microenvironment, and the locally responsive property of IL-12⊂P1 could subsequently re-educate tumor-associated macrophages (TAMs). In particular, our results illustrated the great therapeutic effects derived from the functional conversion of macrophages. Our strategy was to design a microenvironment-responsive material for local macrophage modification to overcome the physiological barrier of solid tumors. The shifting of macrophage phenotypes via IL-12⊂P1 achieved immunomodulation in the microenvironment for cancer therapy, with negligible cytotoxicity. We expect that the functional regulation of TAMs by pH-responsive nanomaterials is a promising therapeutic approach for cancer immunotherapy.
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; University of Chinese Academy of Science (UCAS), No. 19A Yuquan Road, Beijing, China.
authors: Yi
authors: Y
authors: Wang
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; University of Chinese Academy of Science (UCAS), No. 19A Yuquan Road, Beijing, China.
authors: Yao-Xin
authors: YX
authors: Lin
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; University of Chinese Academy of Science (UCAS), No. 19A Yuquan Road, Beijing, China.
authors: Sheng-Lin
authors: SL
authors: Qiao
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; University of Chinese Academy of Science (UCAS), No. 19A Yuquan Road, Beijing, China.
authors: Hong-Wei
authors: HW
authors: An
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; University of Chinese Academy of Science (UCAS), No. 19A Yuquan Road, Beijing, China.
authors: Yang
authors: Y
authors: Ma
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China.
authors: Zeng-Ying
authors: ZY
authors: Qiao
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; University of Chinese Academy of Science (UCAS), No. 19A Yuquan Road, Beijing, China.
authors: R P Yeshan J
authors: RP
authors: Rajapaksha
authors: CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing, China; University of Chinese Academy of Science (UCAS), No. 19A Yuquan Road, Beijing, China. Electronic address: wanghao@nanoctr.cn.
authors: Hao
authors: H
authors: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D065150:Cellular Reprogramming / Q000187:drug effects / Q000276:immunology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000276:immunology*
chemical_list: D003692:Delayed-Action Preparations; D053769:Nanocapsules; D011108:Polymers; D018664:Interleukin-12
keywords: Cancer; Immunotherapy; Macrophage; Nanoparticles; Self-assembly