A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activation

Abstract In recent years, anti-tumor immunity has emerged as a central focus in cancer research, with the rapid advancement of immunotherapy heralding a new era in cancer treatment. Despite the significant potential of immunotherapy, the use of single-agent approaches or limited combination therapie...

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Main Authors: Weizhe Xu, Shiyuan Wang, Jiayi Zhang, Fang Wang, Zhaogang Sun, Bei Liu, Jun Ye, Hongqian Chu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03464-1
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author Weizhe Xu
Shiyuan Wang
Jiayi Zhang
Fang Wang
Zhaogang Sun
Bei Liu
Jun Ye
Hongqian Chu
author_facet Weizhe Xu
Shiyuan Wang
Jiayi Zhang
Fang Wang
Zhaogang Sun
Bei Liu
Jun Ye
Hongqian Chu
author_sort Weizhe Xu
collection DOAJ
description Abstract In recent years, anti-tumor immunity has emerged as a central focus in cancer research, with the rapid advancement of immunotherapy heralding a new era in cancer treatment. Despite the significant potential of immunotherapy, the use of single-agent approaches or limited combination therapies has not consistently yielded optimal therapeutic outcomes. The strategic and controlled integration of diverse immune activation techniques within a single nanoparticle, utilizing a straightforward and universal methodology, continues to present a substantial challenge. Self-assembly, as a simple synthesis method, offers the possibility of combining multiple therapeutic approaches through straightforward means. In this study, we developed a novel approach to construct a biocompatible nanosystem, named Cu-ICG-CpG-FA (CICF), which was synthesized through one-pot coordination-driven self-assembly of Cu2+ ions, CpG oligonucleotides and indocyanine green (ICG), followed by a surface modification with folic acid. Folic acid, as a ligand, can bind to folic acid receptors expressed on the surface of tumor cells. Cu2+ facilitates chemodynamic therapy (CDT) through the Fenton reaction. ICG serves as a therapeutic for photothermal therapy (PTT) and photodynamic therapy (PDT). Moreover, CDT and PTT/PDT can induce immunogenic cell death (ICD), which is further enhanced by the immune-stimulating effect of CpG, thereby improving the tumor immunosuppressive microenvironment. Therefore, CICF provides a simple and efficient approach to synergistic cancer immunotherapy with promising clinical applications. Graphical Abstract
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spelling doaj-art-050b67bb50c84d158ce403721d3d87fb2025-08-20T02:05:42ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123112010.1186/s12951-025-03464-1A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activationWeizhe Xu0Shiyuan Wang1Jiayi Zhang2Fang Wang3Zhaogang Sun4Bei Liu5Jun Ye6Hongqian Chu7Translational Medicine Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical UniversityState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical CollegeTranslational Medicine Center, Beijing Chest Hospital, Capital Medical UniversityTranslational Medicine Center, Beijing Chest Hospital, Capital Medical UniversityTranslational Medicine Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical UniversityCollege of Science, Minzu University of ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical CollegeTranslational Medicine Center, Beijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical UniversityAbstract In recent years, anti-tumor immunity has emerged as a central focus in cancer research, with the rapid advancement of immunotherapy heralding a new era in cancer treatment. Despite the significant potential of immunotherapy, the use of single-agent approaches or limited combination therapies has not consistently yielded optimal therapeutic outcomes. The strategic and controlled integration of diverse immune activation techniques within a single nanoparticle, utilizing a straightforward and universal methodology, continues to present a substantial challenge. Self-assembly, as a simple synthesis method, offers the possibility of combining multiple therapeutic approaches through straightforward means. In this study, we developed a novel approach to construct a biocompatible nanosystem, named Cu-ICG-CpG-FA (CICF), which was synthesized through one-pot coordination-driven self-assembly of Cu2+ ions, CpG oligonucleotides and indocyanine green (ICG), followed by a surface modification with folic acid. Folic acid, as a ligand, can bind to folic acid receptors expressed on the surface of tumor cells. Cu2+ facilitates chemodynamic therapy (CDT) through the Fenton reaction. ICG serves as a therapeutic for photothermal therapy (PTT) and photodynamic therapy (PDT). Moreover, CDT and PTT/PDT can induce immunogenic cell death (ICD), which is further enhanced by the immune-stimulating effect of CpG, thereby improving the tumor immunosuppressive microenvironment. Therefore, CICF provides a simple and efficient approach to synergistic cancer immunotherapy with promising clinical applications. Graphical Abstracthttps://doi.org/10.1186/s12951-025-03464-1Photothermal therapyPhotodynamic therapyChemodynamic therapyImmunotherapySelf-assembly
spellingShingle Weizhe Xu
Shiyuan Wang
Jiayi Zhang
Fang Wang
Zhaogang Sun
Bei Liu
Jun Ye
Hongqian Chu
A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activation
Journal of Nanobiotechnology
Photothermal therapy
Photodynamic therapy
Chemodynamic therapy
Immunotherapy
Self-assembly
title A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activation
title_full A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activation
title_fullStr A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activation
title_full_unstemmed A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activation
title_short A minimalist self-assembly nanosystem for cancer immunotherapy via multiple immune activation
title_sort minimalist self assembly nanosystem for cancer immunotherapy via multiple immune activation
topic Photothermal therapy
Photodynamic therapy
Chemodynamic therapy
Immunotherapy
Self-assembly
url https://doi.org/10.1186/s12951-025-03464-1
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