Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages
Abstract Accurate delineation of glioma infiltrative margins remains a challenge due to the low density of cancer cells in these regions. Here, a hierarchical imaging strategy to define glioma margins by locating the immunosuppressive tumor‐associated macrophages (TAMs) is proposed. A pH ratiometric...
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Language: | English |
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Wiley
2023-10-01
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Series: | Advanced Science |
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Online Access: | https://doi.org/10.1002/advs.202304020 |
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author | Chong Cao Hang Yin Biao Yang Qi Yue Guoqing Wu Meng Gu Yuwen Zhang Yang Fan Xiaoyan Dong Ting Wang Cong Wang Xiao Zhu Ying Mao Xiao‐Yong Zhang Zuhai Lei Cong Li |
author_facet | Chong Cao Hang Yin Biao Yang Qi Yue Guoqing Wu Meng Gu Yuwen Zhang Yang Fan Xiaoyan Dong Ting Wang Cong Wang Xiao Zhu Ying Mao Xiao‐Yong Zhang Zuhai Lei Cong Li |
author_sort | Chong Cao |
collection | DOAJ |
description | Abstract Accurate delineation of glioma infiltrative margins remains a challenge due to the low density of cancer cells in these regions. Here, a hierarchical imaging strategy to define glioma margins by locating the immunosuppressive tumor‐associated macrophages (TAMs) is proposed. A pH ratiometric fluorescent probe CP2‐M that targets immunosuppressive TAMs by binding to mannose receptor (CD206) is developed, and it subsequently senses the acidic phagosomal lumen, resulting in a remarkable fluorescence enhancement. With assistance of CP2‐M, glioma xenografts in mouse models with a tumor‐to‐background ratio exceeding 3.0 for up to 6 h are successfully visualized. Furthermore, by intra‐operatively mapping the pH distribution of exposed tissue after craniotomy, the glioma allograft in rat models is precisely excised. The overall survival of rat models significantly surpasses that achieved using clinically employed fluorescent probes. This work presents a novel strategy for locating glioma margins, thereby improving surgical outcomes for tumors with infiltrative characteristics. |
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institution | Directory Open Access Journal |
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language | English |
last_indexed | 2024-03-11T19:22:23Z |
publishDate | 2023-10-01 |
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spelling | doaj.art-be88871507274e9a9ded088d5e7dfd232023-10-07T03:51:49ZengWileyAdvanced Science2198-38442023-10-011028n/an/a10.1002/advs.202304020Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated MacrophagesChong Cao0Hang Yin1Biao Yang2Qi Yue3Guoqing Wu4Meng Gu5Yuwen Zhang6Yang Fan7Xiaoyan Dong8Ting Wang9Cong Wang10Xiao Zhu11Ying Mao12Xiao‐Yong Zhang13Zuhai Lei14Cong Li15Key Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaSchool of Information Science and Technology Fudan University Shanghai 200438 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaInstitute of Science and Technology for Brain‐Inspired Intelligence MOE Key Laboratory of Computational Neuroscience and Brain‐Inspired Intelligence MOE Frontiers Center for Brain Science Fudan University 220 Handan Road Shanghai 200433 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaInstitute of Science and Technology for Brain‐Inspired Intelligence MOE Key Laboratory of Computational Neuroscience and Brain‐Inspired Intelligence MOE Frontiers Center for Brain Science Fudan University 220 Handan Road Shanghai 200433 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaKey Laboratory of Smart Drug Delivery Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases, Ministry of Education School of Pharmacy Department of Neurosurgery, Huashan Hospital Fudan University Shanghai 201203 ChinaAbstract Accurate delineation of glioma infiltrative margins remains a challenge due to the low density of cancer cells in these regions. Here, a hierarchical imaging strategy to define glioma margins by locating the immunosuppressive tumor‐associated macrophages (TAMs) is proposed. A pH ratiometric fluorescent probe CP2‐M that targets immunosuppressive TAMs by binding to mannose receptor (CD206) is developed, and it subsequently senses the acidic phagosomal lumen, resulting in a remarkable fluorescence enhancement. With assistance of CP2‐M, glioma xenografts in mouse models with a tumor‐to‐background ratio exceeding 3.0 for up to 6 h are successfully visualized. Furthermore, by intra‐operatively mapping the pH distribution of exposed tissue after craniotomy, the glioma allograft in rat models is precisely excised. The overall survival of rat models significantly surpasses that achieved using clinically employed fluorescent probes. This work presents a novel strategy for locating glioma margins, thereby improving surgical outcomes for tumors with infiltrative characteristics.https://doi.org/10.1002/advs.202304020gliomashierarchical strategypH responsive probessurgical navigationstumor‐associated macrophages |
spellingShingle | Chong Cao Hang Yin Biao Yang Qi Yue Guoqing Wu Meng Gu Yuwen Zhang Yang Fan Xiaoyan Dong Ting Wang Cong Wang Xiao Zhu Ying Mao Xiao‐Yong Zhang Zuhai Lei Cong Li Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages Advanced Science gliomas hierarchical strategy pH responsive probes surgical navigations tumor‐associated macrophages |
title | Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages |
title_full | Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages |
title_fullStr | Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages |
title_full_unstemmed | Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages |
title_short | Intra‐Operative Definition of Glioma Infiltrative Margins by Visualizing Immunosuppressive Tumor‐Associated Macrophages |
title_sort | intra operative definition of glioma infiltrative margins by visualizing immunosuppressive tumor associated macrophages |
topic | gliomas hierarchical strategy pH responsive probes surgical navigations tumor‐associated macrophages |
url | https://doi.org/10.1002/advs.202304020 |
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