Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation
Abstract Lack of tumor‐infiltration lymphocytes (TILs) and resistances by overexpressed immunosuppressive cells (principally, myeloid‐derived suppressor cells (MDSCs)) in tumor milieu are two major challenges hindering the effectiveness of immunotherapy for “immune‐cold” tumors. In addition, the nat...
Main Authors: | , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Wiley
2020-09-01
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Series: | Advanced Science |
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Online Access: | https://doi.org/10.1002/advs.202000411 |
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doaj-91aa2ce0f1df49aba5ee8eb3a050f5eb |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Qinjun Chen Yongqing He Yu Wang Chao Li Yujie Zhang Qin Guo Yiwen Zhang Yongchao Chu Peixin Liu Hongyi Chen Zheng Zhou Wenxi Zhou Zhenhao Zhao Xiaomin Li Tao Sun Chen Jiang |
spellingShingle |
Qinjun Chen Yongqing He Yu Wang Chao Li Yujie Zhang Qin Guo Yiwen Zhang Yongchao Chu Peixin Liu Hongyi Chen Zheng Zhou Wenxi Zhou Zhenhao Zhao Xiaomin Li Tao Sun Chen Jiang Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation Advanced Science antitumor immune responses immunogenic cell death immunosuppression metal–organic frameworks penetration |
author_facet |
Qinjun Chen Yongqing He Yu Wang Chao Li Yujie Zhang Qin Guo Yiwen Zhang Yongchao Chu Peixin Liu Hongyi Chen Zheng Zhou Wenxi Zhou Zhenhao Zhao Xiaomin Li Tao Sun Chen Jiang |
author_sort |
Qinjun Chen |
title |
Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation |
title_short |
Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation |
title_full |
Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation |
title_fullStr |
Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation |
title_full_unstemmed |
Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment Reeducation |
title_sort |
penetrable nanoplatform for “cold” tumor immune microenvironment reeducation |
publisher |
Wiley |
series |
Advanced Science |
issn |
2198-3844 |
publishDate |
2020-09-01 |
description |
Abstract Lack of tumor‐infiltration lymphocytes (TILs) and resistances by overexpressed immunosuppressive cells (principally, myeloid‐derived suppressor cells (MDSCs)) in tumor milieu are two major challenges hindering the effectiveness of immunotherapy for “immune‐cold” tumors. In addition, the natural physical barrier existing in solid cancer also limits deeper delivery of drugs. Here, a tumor‐targeting and light‐responsive‐penetrable nanoplatform (Apt/PDGs^s@pMOF) is developed to elicit intratumoral infiltration of cytotoxic T cells (CTLs) and reeducate immunosuppressive microenvironment simultaneously. In particular, porphyrinic metal–organic framework (pMOF)–based photodynamic therapy (PDT) induces tumor immunogenic cell death (ICD) to promote CTLs intratumoral infiltration and hot “immune‐cold” tumor. Upon being triggered by PDT, the nearly 10 nm adsorbed drug‐loaded dendrimer de‐shields from the nanoplatform and spreads into the deeper tumor, eliminating MDSCs and reversing immunosuppression, eventually reinforcing immune response. Meanwhile, the designed nanoplatform also has a systemic MDSC inhibition effect and moderate improvement of overall antitumor immune responses, resulting in effective suppression of distal tumors within less significant immune‐related adverse effects (irAEs) induced. |
topic |
antitumor immune responses immunogenic cell death immunosuppression metal–organic frameworks penetration |
url |
https://doi.org/10.1002/advs.202000411 |
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1724582678355771392 |
spelling |
doaj-91aa2ce0f1df49aba5ee8eb3a050f5eb2020-11-25T03:28:48ZengWileyAdvanced Science2198-38442020-09-01717n/an/a10.1002/advs.202000411Penetrable Nanoplatform for “Cold” Tumor Immune Microenvironment ReeducationQinjun Chen0Yongqing He1Yu Wang2Chao Li3Yujie Zhang4Qin Guo5Yiwen Zhang6Yongchao Chu7Peixin Liu8Hongyi Chen9Zheng Zhou10Wenxi Zhou11Zhenhao Zhao12Xiaomin Li13Tao Sun14Chen Jiang15Key Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaDepartment of Chemistry and Laboratory of Advanced Materials Fudan University Shanghai 200433 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaKey Laboratory of Smart Drug Delivery (Ministry of Education) State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Science Department of Pharmaceutics School of Pharmacy Research Center on Aging and Medicine Fudan University Shanghai 201203 P. R. ChinaAbstract Lack of tumor‐infiltration lymphocytes (TILs) and resistances by overexpressed immunosuppressive cells (principally, myeloid‐derived suppressor cells (MDSCs)) in tumor milieu are two major challenges hindering the effectiveness of immunotherapy for “immune‐cold” tumors. In addition, the natural physical barrier existing in solid cancer also limits deeper delivery of drugs. Here, a tumor‐targeting and light‐responsive‐penetrable nanoplatform (Apt/PDGs^s@pMOF) is developed to elicit intratumoral infiltration of cytotoxic T cells (CTLs) and reeducate immunosuppressive microenvironment simultaneously. In particular, porphyrinic metal–organic framework (pMOF)–based photodynamic therapy (PDT) induces tumor immunogenic cell death (ICD) to promote CTLs intratumoral infiltration and hot “immune‐cold” tumor. Upon being triggered by PDT, the nearly 10 nm adsorbed drug‐loaded dendrimer de‐shields from the nanoplatform and spreads into the deeper tumor, eliminating MDSCs and reversing immunosuppression, eventually reinforcing immune response. Meanwhile, the designed nanoplatform also has a systemic MDSC inhibition effect and moderate improvement of overall antitumor immune responses, resulting in effective suppression of distal tumors within less significant immune‐related adverse effects (irAEs) induced.https://doi.org/10.1002/advs.202000411antitumor immune responsesimmunogenic cell deathimmunosuppressionmetal–organic frameworkspenetration |