An Endoplasmic Reticulum‐Targeting and Calcium Metabolism‐Disrupting Nanodrug Enhances Tumor Photodynamic Immunotherapy

Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Poly(Ethylene Glycol)‐Modified Catalase Blocking Reactive Oxygen Species for the Treatment of Hepatic Ischemia

Macromolecular Rapid Communications, Journal Year: 2025, Volume and Issue: unknown

Published: May 26, 2025

Abstract Hepatic ischemia‐reperfusion injury (IRI) is a severe clinical condition often leading to liver dysfunction due oxidative stress and inflammatory responses. This study investigates the therapeutic potential of polyethylene glycol (PEG)‐modified catalase (CAT) in alleviating damage associated with hepatic IRI. Catalase, an enzyme that decomposes hydrogen peroxide into water oxygen, modified PEG enhance its stability, bioavailability, prolong half‐life vivo. PEGylation significantly improved pharmacokinetics CAT by extending circulation enhancing stability against enzymatic degradation. Both vitro vivo experiments demonstrated PEGylated (CAT‐PEG) efficiently reduced reactive oxygen species (ROS) levels, mitigated stress, function post‐reperfusion. These findings suggest CAT‐PEG promising strategy for treating IRI, broader applications transplantation other conditions involving damage.

Language: Английский