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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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2023-10-01
Series:Advanced Science
Subjects:
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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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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