DataVXAdvanced Functional MaterialsPaper
journal article·2026-05

Immune‐Engineered Hydrogels Combat Orthotopic and Metastatic Cancer via Hypoxia‐Relieved Photodynamic Therapy and Ferroptotic Cell Death

Cong Fu, Yuanyuan Cao, Yijun Mei, Qiaqia Xiao, Jingyi Hu, Zhencheng Gao, Xueyu Gao, Yi Hou, Fei Zhang, Guangda Zhu, Chao Zhang, Yue Yin, Hening Liu, Ruiyue Chen, Jinying Zhang, Xin Han, Yujun Song, Wei Wang, Lu Tang

Advanced Functional Materials· Volume 36· Issue 42
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Source abstract

Abstract

ABSTRACT Hypoxia severely impairs photodynamic therapy (PDT) by limiting oxygen availability and activating HIF‐1α‐mediated immunosuppressive pathways. Herein, we develop fully functional immune hydrogels (AV@PFgel) that synergistically integrate hypoxia relief, ferroptosis induction, and violet phosphorus nanosheet (VPN)‐induced PDT within a single therapeutic platform to potentiate antitumor immunity. The dual‐crosslinked AV@PFgel degrades in acidic tumor microenvironment (TME) to enable oxygen generation and Fenton reaction‐mediated ferroptosis through released PolyMet, Fe 3+ , and acriflavine (ACF)‐loaded VPN, jointly promoting immunogenic cell death (ICD). VPN, acting as a potent photosensitizer, triggers PDT for direct tumor ablation and ICD induction, whereas ACF‐mediated HIF‐1α inhibition counteracts hypoxia‐associated immunosuppression. Notably, AV@PFgel reprograms the TME into an immunostimulatory state, eliciting durable local and systemic antitumor immune responses. Consequently, a single intratumoral administration of AV@PFgel combined with regular laser irradiation markedly suppresses primary and metastatic triple‐negative breast cancer, highlighting its translational promise for long‐term cancer immunotherapy. Collectively, this work presents a versatile and integrated strategy to overcome the hypoxia barrier while coordinately activating both innate and adaptive immune responses, paving the way for advanced cancer immunotherapy with improved and durable efficacy.
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Research context

PolymersNanomaterials

OpenAlex topics: Nanoplatforms for cancer theranostics · Cancer, Hypoxia, and Metabolism · Ferroptosis and cancer prognosis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Natural Medicines Department of Pharmaceutics School of Pharmacy China Pharmaceutical University Nanjing P. R. China

NMPA Key Laboratory for Research and Evaluation of Cosmetics China Pharmaceutical University Nanjing P. R. China

Wuxi Research Center for Innovative Medicines and Life Health Wuxi Innovation Research Institute of China Pharmaceutical University Wuxi P. R. China

Centre for Translational Bone Joint and Soft Tissue Research TU Dresden Dresden Germany

Leibniz‐Institut für Polymerforschung Dresden e.V. (IPF) Dresden Germany

Research Center for Materials Architectures, and Integration of Nanomembranes (Main) TU Chemnitz Chemnitz Germany

Engler‐Bunte‐Institut Water Chemistry and Water Technology Karlsruhe Institute of Technology Karlsruhe Germany

College of Engineering and Applied Sciences State Key Laboratory of Analytical Chemistry for Life Science National Laboratory of Solid State Microstructures Nanjing University Nanjing P. R. China

State Key Laboratory of Electrical Insulation and Power Equipment Center of Nanomaterials for Renewable Energy School of Electrical Engineering Xi'an Jiaotong University Xi'an P. R. China

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of Medicine & Holistic Integrative Medicine Jiangsu Joint International Research Laboratory of Chinese Medicine and Regenerative Medicine Nanjing University of Chinese Medicine Nanjing P. R. China

Institute for Experimental Molecular Imaging Uniklinik RWTH Aachen and Helmholtz Institute for Biomedical Engineering RWTH Aachen University Aachen Germany

Funding

National Natural Science Foundation of China · Six Talent Peaks Project in Jiangsu Province

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