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Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy
Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy e...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914428/ https://www.ncbi.nlm.nih.gov/pubmed/29732051 http://dx.doi.org/10.1039/c7sc04853j |
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author | Zhao, Pengfei Wang, Yonghui Kang, Xuejia Wu, Aihua Yin, Weimin Tang, Yisi Wang, Jinyu Zhang, Meng Duan, Yifei Huang, Yongzhuo |
author_facet | Zhao, Pengfei Wang, Yonghui Kang, Xuejia Wu, Aihua Yin, Weimin Tang, Yisi Wang, Jinyu Zhang, Meng Duan, Yifei Huang, Yongzhuo |
author_sort | Zhao, Pengfei |
collection | PubMed |
description | Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity. We demonstrated that the albumin nanoparticles modified with dual ligands, a transferrin receptor (TfR)-binding peptide T12 and mannose, efficiently passed through the BBB via the nutrient transporters (i.e., TfR and the albumin-binding receptor SPARC) that were both overexpressed in the BBB and glioma cells, thus achieving biomimetic delivery to glioma. Importantly, after penetrating the BBB, this system can take advantage of the overexpression of the SPARC and mannose receptors on TAM2, thus also targeting the protumor TAM2. With the codelivery disulfiram/copper complex and regorafenib, the system efficiently inhibited the glioma cell proliferation and successfully “re-educated” the protumor TAM2 towards antitumor TAM1. The treatment efficacy was examined in the glioma-bearing nude mice and immunocompetent mice. It showed this system yielded an enhanced treatment outcome, owing to the synergistic combination of chemotherapy and macrophage-directed immunotherapy. The importance of this delivery and therapeutic strategy was to remodel the immune microenvironment and reprogram TAM and trigger macrophage-directed anti-glioma immunotherapy via the interplay of the TAM, Treg, and CD8(+) T cells and the effector cytokines. The albumin-based biomimetic brain delivery also provides a promising method for the pharmacotherapy of brain diseases. |
format | Online Article Text |
id | pubmed-5914428 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-59144282018-05-04 Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy Zhao, Pengfei Wang, Yonghui Kang, Xuejia Wu, Aihua Yin, Weimin Tang, Yisi Wang, Jinyu Zhang, Meng Duan, Yifei Huang, Yongzhuo Chem Sci Chemistry Tumor-associated macrophages (TAMs) are the major components in the tumor microenvironment (TME). The polarization from the protumor M2 (TAM2) to antitumor M1 (TAM1) phenotype can not only lift the immunosuppressive constraints and elicit cytotoxic T-cell immunity but also augment the chemotherapy efficacy. However, the treatment feasibility by TAM modulation in brain tumors and the mechanisms remained unknown. A dual-targeting biomimetic codelivery and treatment strategy was developed for anti-glioma activity. We demonstrated that the albumin nanoparticles modified with dual ligands, a transferrin receptor (TfR)-binding peptide T12 and mannose, efficiently passed through the BBB via the nutrient transporters (i.e., TfR and the albumin-binding receptor SPARC) that were both overexpressed in the BBB and glioma cells, thus achieving biomimetic delivery to glioma. Importantly, after penetrating the BBB, this system can take advantage of the overexpression of the SPARC and mannose receptors on TAM2, thus also targeting the protumor TAM2. With the codelivery disulfiram/copper complex and regorafenib, the system efficiently inhibited the glioma cell proliferation and successfully “re-educated” the protumor TAM2 towards antitumor TAM1. The treatment efficacy was examined in the glioma-bearing nude mice and immunocompetent mice. It showed this system yielded an enhanced treatment outcome, owing to the synergistic combination of chemotherapy and macrophage-directed immunotherapy. The importance of this delivery and therapeutic strategy was to remodel the immune microenvironment and reprogram TAM and trigger macrophage-directed anti-glioma immunotherapy via the interplay of the TAM, Treg, and CD8(+) T cells and the effector cytokines. The albumin-based biomimetic brain delivery also provides a promising method for the pharmacotherapy of brain diseases. Royal Society of Chemistry 2018-01-31 /pmc/articles/PMC5914428/ /pubmed/29732051 http://dx.doi.org/10.1039/c7sc04853j Text en This journal is © The Royal Society of Chemistry 2018 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0) |
spellingShingle | Chemistry Zhao, Pengfei Wang, Yonghui Kang, Xuejia Wu, Aihua Yin, Weimin Tang, Yisi Wang, Jinyu Zhang, Meng Duan, Yifei Huang, Yongzhuo Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy |
title | Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy
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title_full | Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy
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title_fullStr | Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy
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title_full_unstemmed | Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy
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title_short | Dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy
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title_sort | dual-targeting biomimetic delivery for anti-glioma activity via remodeling the tumor microenvironment and directing macrophage-mediated immunotherapy |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5914428/ https://www.ncbi.nlm.nih.gov/pubmed/29732051 http://dx.doi.org/10.1039/c7sc04853j |
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