An Endoplasmic Reticulum‐Targeting and Calcium Metabolism‐Disrupting Nanodrug Enhances Tumor Photodynamic Immunotherapy DOI Open Access
Shiyu Liang,

Gulijiayina Jiaerheng,

Chengjie Huang

и другие.

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 16, 2025

Abstract The inefficient clearance of deep tumors and metastatic lesions greatly hinders the clinical applications photodynamic therapy (PDT). Inducing robust immunogenic cell death (ICD) is crucial for improving PDT outcomes, as ICD‐mediated T‐cell adaptive immune responses suppress tumor recurrence metastasis. Sustained endoplasmic reticulum (ER) stress essential activating ICD, however, inadequate photosensitizer enrichment in ER cell‐protective mechanisms, such unfolded protein response (UPR) antioxidant defense, often result insufficient ineffective ICD. To overcome these challenges, PPRK@MTO, a nanodrug co‐assembled from ER‐targeting chimeric peptide PpIX‐PEG 8 ‐RKR‐KDEL (PPRK) mitochondrial calcium uniporter (MCU) inhibitor mitoxantrone (MTO) developed. Upon laser irradiation, PPRK generates reactive oxygen species (ROS) situ, inducing strong promoting Meanwhile, MTO inhibits MCU, reducing influx energy supply UPR glutathione biosynthesis, thereby amplifying efficacy enhancing antitumor response. PPRK@MTO demonstrats potent suppression vivo prolonged survival 4T1 tumor‐bearing mice with single administration. This metabolism‐disrupting provides promising strategy high‐efficiency immunotherapy.

Язык: Английский

An Endoplasmic Reticulum‐Targeting and Calcium Metabolism‐Disrupting Nanodrug Enhances Tumor Photodynamic Immunotherapy DOI Open Access
Shiyu Liang,

Gulijiayina Jiaerheng,

Chengjie Huang

и другие.

Advanced Functional Materials, Год журнала: 2025, Номер unknown

Опубликована: Март 16, 2025

Abstract The inefficient clearance of deep tumors and metastatic lesions greatly hinders the clinical applications photodynamic therapy (PDT). Inducing robust immunogenic cell death (ICD) is crucial for improving PDT outcomes, as ICD‐mediated T‐cell adaptive immune responses suppress tumor recurrence metastasis. Sustained endoplasmic reticulum (ER) stress essential activating ICD, however, inadequate photosensitizer enrichment in ER cell‐protective mechanisms, such unfolded protein response (UPR) antioxidant defense, often result insufficient ineffective ICD. To overcome these challenges, PPRK@MTO, a nanodrug co‐assembled from ER‐targeting chimeric peptide PpIX‐PEG 8 ‐RKR‐KDEL (PPRK) mitochondrial calcium uniporter (MCU) inhibitor mitoxantrone (MTO) developed. Upon laser irradiation, PPRK generates reactive oxygen species (ROS) situ, inducing strong promoting Meanwhile, MTO inhibits MCU, reducing influx energy supply UPR glutathione biosynthesis, thereby amplifying efficacy enhancing antitumor response. PPRK@MTO demonstrats potent suppression vivo prolonged survival 4T1 tumor‐bearing mice with single administration. This metabolism‐disrupting provides promising strategy high‐efficiency immunotherapy.

Язык: Английский

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