An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy

Abstract Photodynamic therapy holds great potentials in cancer treatment, yet its effectiveness in hypoxic solid tumor is limited by the oxygen‐dependence and insufficient oxidative potential of conventional type II reactive oxygen species (ROS). Herein, the study reports a supramolecular photosensi...

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Main Authors: Jingtian Zhang, Di Jiao, Xinwen Qi, Yufan Zhang, Xiaoang Liu, Tengwu Pan, Heqi Gao, Zhaoyun Liu, Dan Ding, Guangxue Feng
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202410405
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author Jingtian Zhang
Di Jiao
Xinwen Qi
Yufan Zhang
Xiaoang Liu
Tengwu Pan
Heqi Gao
Zhaoyun Liu
Dan Ding
Guangxue Feng
author_facet Jingtian Zhang
Di Jiao
Xinwen Qi
Yufan Zhang
Xiaoang Liu
Tengwu Pan
Heqi Gao
Zhaoyun Liu
Dan Ding
Guangxue Feng
author_sort Jingtian Zhang
collection DOAJ
description Abstract Photodynamic therapy holds great potentials in cancer treatment, yet its effectiveness in hypoxic solid tumor is limited by the oxygen‐dependence and insufficient oxidative potential of conventional type II reactive oxygen species (ROS). Herein, the study reports a supramolecular photosensitizer, BSA@TPE‐BT‐SCT NPs, through encapsulating aggregation‐enhanced emission photosensitizer by bovine serum albumin (BSA) to significantly enhance ROS, particularly less oxygen‐dependent type I ROS for photodynamic immunotherapy. The abundant type I ROS generated by BSA@TPE‐BT‐SCT NPs induce multiple forms of programmed cell death, including apoptosis, pyroptosis, and ferroptosis. These multifaceted cell deaths synergistically facilitate the release of damage‐associated molecular patterns and antitumor cytokines, thereby provoking robust antitumor immunity. Both in vitro and in vivo experiments confirmed that BSA@TPE‐BT‐SCT NPs elicited the immunogenic cell death, enhance dendritic cell maturation, activate T cell, and reduce myeloid‐derived suppressor cells, leading to the inhibition of both primary and distant tumors. Additionally, BSA@TPE‐BT‐SCP NPs also exhibited excellent antitumor performance in a humanized mice model, evidenced by a reduction in senescent T cells among these activated T cells. The findings advance the development of robust type I photosensitizers and unveil the important role of type I ROS in enhancing multifaceted tumor cell deaths and antitumor immunogenicity.
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spelling doaj-art-e488d6a3a8ca4eb28b861d518b8a03fd2025-08-20T03:24:44ZengWileyAdvanced Science2198-38442025-03-01129n/an/a10.1002/advs.202410405An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic ImmunotherapyJingtian Zhang0Di Jiao1Xinwen Qi2Yufan Zhang3Xiaoang Liu4Tengwu Pan5Heqi Gao6Zhaoyun Liu7Dan Ding8Guangxue Feng9Frontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaFrontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaFrontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaFrontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaFrontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaFrontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaFrontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaDepartment of Hematology Tianjin Medical University General Hospital Tianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control Tianjin Institute of Hematology Tianjin 300052 ChinaFrontiers Science Center for Cell Responses State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials Ministry of Education and College of Life Sciences Nankai University Tianjin 300071 ChinaGuangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering AIE Institute South China University of Technology Guangzhou 510640 ChinaAbstract Photodynamic therapy holds great potentials in cancer treatment, yet its effectiveness in hypoxic solid tumor is limited by the oxygen‐dependence and insufficient oxidative potential of conventional type II reactive oxygen species (ROS). Herein, the study reports a supramolecular photosensitizer, BSA@TPE‐BT‐SCT NPs, through encapsulating aggregation‐enhanced emission photosensitizer by bovine serum albumin (BSA) to significantly enhance ROS, particularly less oxygen‐dependent type I ROS for photodynamic immunotherapy. The abundant type I ROS generated by BSA@TPE‐BT‐SCT NPs induce multiple forms of programmed cell death, including apoptosis, pyroptosis, and ferroptosis. These multifaceted cell deaths synergistically facilitate the release of damage‐associated molecular patterns and antitumor cytokines, thereby provoking robust antitumor immunity. Both in vitro and in vivo experiments confirmed that BSA@TPE‐BT‐SCT NPs elicited the immunogenic cell death, enhance dendritic cell maturation, activate T cell, and reduce myeloid‐derived suppressor cells, leading to the inhibition of both primary and distant tumors. Additionally, BSA@TPE‐BT‐SCP NPs also exhibited excellent antitumor performance in a humanized mice model, evidenced by a reduction in senescent T cells among these activated T cells. The findings advance the development of robust type I photosensitizers and unveil the important role of type I ROS in enhancing multifaceted tumor cell deaths and antitumor immunogenicity.https://doi.org/10.1002/advs.202410405ferroptosisimmunogenic cell deathprogrammed cell deathpyroptosisType I photodynamic therapy
spellingShingle Jingtian Zhang
Di Jiao
Xinwen Qi
Yufan Zhang
Xiaoang Liu
Tengwu Pan
Heqi Gao
Zhaoyun Liu
Dan Ding
Guangxue Feng
An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy
Advanced Science
ferroptosis
immunogenic cell death
programmed cell death
pyroptosis
Type I photodynamic therapy
title An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy
title_full An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy
title_fullStr An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy
title_full_unstemmed An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy
title_short An Albumin‐Photosensitizer Supramolecular Assembly with Type I ROS‐Induced Multifaceted Tumor Cell Deaths for Photodynamic Immunotherapy
title_sort albumin photosensitizer supramolecular assembly with type i ros induced multifaceted tumor cell deaths for photodynamic immunotherapy
topic ferroptosis
immunogenic cell death
programmed cell death
pyroptosis
Type I photodynamic therapy
url https://doi.org/10.1002/advs.202410405
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