Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of Glioblastoma

Abstract It is a big challenge for precision therapy of glioblastoma, mainly due to the existence of blood–brain barrier (BBB), tumor immunosuppressive microenvironment (TIM), and lack of efficient treatment paradigms. Herein, a theranostic nanoplatform for the second near‐infrared window (NIR‐II) f...

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Main Authors: Pengfei Chen, Yue Liu, Haiyan Huang, Menglong Li, Hui Xie, Shubham Roy, Jingsi Gu, Jian Jin, Kai Deng, Lixin Du, Bing Guo
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202500131
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author Pengfei Chen
Yue Liu
Haiyan Huang
Menglong Li
Hui Xie
Shubham Roy
Jingsi Gu
Jian Jin
Kai Deng
Lixin Du
Bing Guo
author_facet Pengfei Chen
Yue Liu
Haiyan Huang
Menglong Li
Hui Xie
Shubham Roy
Jingsi Gu
Jian Jin
Kai Deng
Lixin Du
Bing Guo
author_sort Pengfei Chen
collection DOAJ
description Abstract It is a big challenge for precision therapy of glioblastoma, mainly due to the existence of blood–brain barrier (BBB), tumor immunosuppressive microenvironment (TIM), and lack of efficient treatment paradigms. Herein, a theranostic nanoplatform for the second near‐infrared window (NIR‐II) fluorescence imaging‐guided membrane‐targeted mild photothermal‐immunotherapy of glioblastoma using genetically engineered CSF1R/IL12‐macrophage membrane (MM)‐liposome hybrid nanovesicles, is reported. By mimicking lipophilic membrane probe (Dil) with octadecyl chains, a NIR‐II emissive photothermal dye (IRC18), which realizes labeling of nanovesicle lipid bilayers for biodistribution tracing, glioblastoma diagnosis, and molecular imaging of tumoral microenvironment, is synthesized. Importantly, MM and c‐RGD‐decorated liposome together offer BBB crossing, tumor targeting, and long‐term circulation; while, the genetically overexpressed CSF1R and IL12 on MM surface contribute to effective modulation of M2‐to‐M1 macrophage repolarization and local promotion of T cell cytotoxicity in glioblastoma microenvironment, respectively. Notably, through membrane fusion, IRC18 dyes translocate from nanovesicle lipid bilayers to glioblastoma membranes, which achieve membrane‐targeted mild photothermal therapy to ablate primary tumor and induce immunogenic cell death to promote antigen presentation. More importantly, the combined blockade of the CSF1‐CSF1R axis and IL‐12 enrichment not only reprograms the tumor microenvironment through macrophage M1 repolarization but also activates cytotoxic T cells, ultimately achieving complete glioblastoma eradication. This research provides an efficient theranostic paradigm for glioblastoma treatment.
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spelling doaj-art-e83b65fc96f242118e7699581ae981bf2025-08-20T02:10:19ZengWileyAdvanced Science2198-38442025-06-011223n/an/a10.1002/advs.202500131Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of GlioblastomaPengfei Chen0Yue Liu1Haiyan Huang2Menglong Li3Hui Xie4Shubham Roy5Jingsi Gu6Jian Jin7Kai Deng8Lixin Du9Bing Guo10Department of Traumatic Orthopedics Shenzhen Longhua District Central Hospital Shenzhen 518110 ChinaSchool of Science Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application Harbin Institute of Technology Shenzhen 518055 ChinaSchool of Science Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application Harbin Institute of Technology Shenzhen 518055 ChinaSchool of Science Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application Harbin Institute of Technology Shenzhen 518055 ChinaChengdu Institute of Organic Chemistry Chinese Academy of Sciences Chengdu 610041 ChinaSchool of Science Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application Harbin Institute of Technology Shenzhen 518055 ChinaEducation Center and Experiments and Innovations Harbin Institute of Technology Shenzhen 518055 ChinaEducation Center and Experiments and Innovations Harbin Institute of Technology Shenzhen 518055 ChinaDepartment of Traumatic Orthopedics Shenzhen Longhua District Central Hospital Shenzhen 518110 ChinaDepartment of Medical Imaging Shenzhen Longhua District Key Laboratory of Neuroimaging Shenzhen Longhua District Central Hospital Shenzhen 518110 ChinaSchool of Science Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application Harbin Institute of Technology Shenzhen 518055 ChinaAbstract It is a big challenge for precision therapy of glioblastoma, mainly due to the existence of blood–brain barrier (BBB), tumor immunosuppressive microenvironment (TIM), and lack of efficient treatment paradigms. Herein, a theranostic nanoplatform for the second near‐infrared window (NIR‐II) fluorescence imaging‐guided membrane‐targeted mild photothermal‐immunotherapy of glioblastoma using genetically engineered CSF1R/IL12‐macrophage membrane (MM)‐liposome hybrid nanovesicles, is reported. By mimicking lipophilic membrane probe (Dil) with octadecyl chains, a NIR‐II emissive photothermal dye (IRC18), which realizes labeling of nanovesicle lipid bilayers for biodistribution tracing, glioblastoma diagnosis, and molecular imaging of tumoral microenvironment, is synthesized. Importantly, MM and c‐RGD‐decorated liposome together offer BBB crossing, tumor targeting, and long‐term circulation; while, the genetically overexpressed CSF1R and IL12 on MM surface contribute to effective modulation of M2‐to‐M1 macrophage repolarization and local promotion of T cell cytotoxicity in glioblastoma microenvironment, respectively. Notably, through membrane fusion, IRC18 dyes translocate from nanovesicle lipid bilayers to glioblastoma membranes, which achieve membrane‐targeted mild photothermal therapy to ablate primary tumor and induce immunogenic cell death to promote antigen presentation. More importantly, the combined blockade of the CSF1‐CSF1R axis and IL‐12 enrichment not only reprograms the tumor microenvironment through macrophage M1 repolarization but also activates cytotoxic T cells, ultimately achieving complete glioblastoma eradication. This research provides an efficient theranostic paradigm for glioblastoma treatment.https://doi.org/10.1002/advs.202500131biomimetic strategyglioblastomaimmunotherapyNIR‐II fluorescence imagingphotothermal therapy
spellingShingle Pengfei Chen
Yue Liu
Haiyan Huang
Menglong Li
Hui Xie
Shubham Roy
Jingsi Gu
Jian Jin
Kai Deng
Lixin Du
Bing Guo
Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of Glioblastoma
Advanced Science
biomimetic strategy
glioblastoma
immunotherapy
NIR‐II fluorescence imaging
photothermal therapy
title Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of Glioblastoma
title_full Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of Glioblastoma
title_fullStr Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of Glioblastoma
title_full_unstemmed Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of Glioblastoma
title_short Genetically Engineered IL12/CSF1R‐Macrophage Membrane‐Liposome Hybrid Nanovesicles for NIR‐II Fluorescence Imaging‐Guided and Membrane‐Targeted Mild Photothermal‐Immunotherapy of Glioblastoma
title_sort genetically engineered il12 csf1r macrophage membrane liposome hybrid nanovesicles for nir ii fluorescence imaging guided and membrane targeted mild photothermal immunotherapy of glioblastoma
topic biomimetic strategy
glioblastoma
immunotherapy
NIR‐II fluorescence imaging
photothermal therapy
url https://doi.org/10.1002/advs.202500131
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