ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy

Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained in solid tumors due to the immunosuppressive tumor microenvironment (TME). Reactive oxygen species (ROS), which exhibit dual regulatory roles in the TME by regulating immunogenic cell death (ICD) and r...

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Main Authors: Yuan-Yuan Fan, Hong Wu, Chuan Xu
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/17/7/886
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author Yuan-Yuan Fan
Hong Wu
Chuan Xu
author_facet Yuan-Yuan Fan
Hong Wu
Chuan Xu
author_sort Yuan-Yuan Fan
collection DOAJ
description Despite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained in solid tumors due to the immunosuppressive tumor microenvironment (TME). Reactive oxygen species (ROS), which exhibit dual regulatory roles in the TME by regulating immunogenic cell death (ICD) and reprogramming immune cell functionality, have emerged as a pivotal therapeutic target. Nano-enabled drug delivery systems present distinct advantages for TME modulation due to their structural versatility, tumor-specific targeting precision, and spatiotemporally controlled drug release. In particular, ROS-responsive nanoplatforms demonstrate multifaceted immunomodulatory potential by synergistically restoring ICD and remodeling immunosuppressive immune cell phenotypes within the TME. These platforms further amplify the therapeutic outcomes of conventional modalities including chemotherapy, radiotherapy, and photodynamic therapy (PDT) through ROS-mediated sensitization mechanisms. This review comprehensively examines recent breakthroughs in ROS-responsive nanosystems for antitumor immunotherapy, emphasizing their mechanistic interplay with TME components and clinical translation potential. Herein, we provide a framework for developing integrated therapeutic strategies to overcome the current limitations in cancer immunotherapy.
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spelling doaj-art-72785d1f3a384adf8a1990aa84bdc4662025-08-20T03:32:15ZengMDPI AGPharmaceutics1999-49232025-07-0117788610.3390/pharmaceutics17070886ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer ImmunotherapyYuan-Yuan Fan0Hong Wu1Chuan Xu2Chengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaDepartment of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, ChinaChengdu University of Traditional Chinese Medicine, Chengdu 610072, ChinaDespite remarkable advancements in cancer immunotherapy, its clinical efficacy remains constrained in solid tumors due to the immunosuppressive tumor microenvironment (TME). Reactive oxygen species (ROS), which exhibit dual regulatory roles in the TME by regulating immunogenic cell death (ICD) and reprogramming immune cell functionality, have emerged as a pivotal therapeutic target. Nano-enabled drug delivery systems present distinct advantages for TME modulation due to their structural versatility, tumor-specific targeting precision, and spatiotemporally controlled drug release. In particular, ROS-responsive nanoplatforms demonstrate multifaceted immunomodulatory potential by synergistically restoring ICD and remodeling immunosuppressive immune cell phenotypes within the TME. These platforms further amplify the therapeutic outcomes of conventional modalities including chemotherapy, radiotherapy, and photodynamic therapy (PDT) through ROS-mediated sensitization mechanisms. This review comprehensively examines recent breakthroughs in ROS-responsive nanosystems for antitumor immunotherapy, emphasizing their mechanistic interplay with TME components and clinical translation potential. Herein, we provide a framework for developing integrated therapeutic strategies to overcome the current limitations in cancer immunotherapy.https://www.mdpi.com/1999-4923/17/7/886reactive oxygen speciesROS-responsive drug deliverytumor microenvironmentimmunogenic cell deathantitumor therapy
spellingShingle Yuan-Yuan Fan
Hong Wu
Chuan Xu
ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy
Pharmaceutics
reactive oxygen species
ROS-responsive drug delivery
tumor microenvironment
immunogenic cell death
antitumor therapy
title ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy
title_full ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy
title_fullStr ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy
title_full_unstemmed ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy
title_short ROS-Responsive Nanoplatforms for Targeted Tumor Immunomodulation: A Paradigm Shift in Precision Cancer Immunotherapy
title_sort ros responsive nanoplatforms for targeted tumor immunomodulation a paradigm shift in precision cancer immunotherapy
topic reactive oxygen species
ROS-responsive drug delivery
tumor microenvironment
immunogenic cell death
antitumor therapy
url https://www.mdpi.com/1999-4923/17/7/886
work_keys_str_mv AT yuanyuanfan rosresponsivenanoplatformsfortargetedtumorimmunomodulationaparadigmshiftinprecisioncancerimmunotherapy
AT hongwu rosresponsivenanoplatformsfortargetedtumorimmunomodulationaparadigmshiftinprecisioncancerimmunotherapy
AT chuanxu rosresponsivenanoplatformsfortargetedtumorimmunomodulationaparadigmshiftinprecisioncancerimmunotherapy