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Talaporfin Sodium as a Clinically Translatable Radiosensitizer in Radiodynamic Therapy
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Talaporfin Sodium as a Clinically Translatable Radiosensitizer in Radiodynamic Therapy
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Journal Article
Talaporfin Sodium as a Clinically Translatable Radiosensitizer in Radiodynamic Therapy
2025
Overview
Talaporfin sodium (mono-L-aspartyl chlorin e6; NPe6), a second-generation photosensitizer, is clinically used in photodynamic therapy (PDT). It accumulates preferentially in tumors and exhibits deep tissue penetration, rapid systemic clearance, and minimal photosensitivity. However, treatment of deep-seated malignancies remains challenging. Here, we demonstrate that talaporfin sodium undergoes physicochemical reactions with X-rays to generate reactive oxygen species, a mechanism analogous to that of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX in radiodynamic therapy (RDT). To evaluate its therapeutic efficacy, we employed a pancreatic cancer xenograft model using MIA PaCa-2 cells in mice. Talaporfin sodium was administered intravenously 2 h before X-ray exposure, followed by fractionated X-ray irradiation (3 Gy daily for 3 consecutive days). Talaporfin-mediated RDT significantly inhibited tumor growth compared with radiation therapy alone. Furthermore, an exploratory RNA-seq analysis of xenografts revealed transcriptional signatures of stress and immune activation, suggesting that talaporfin-mediated RDT enhances oxidative and immunogenic responses within the tumor microenvironment. These findings highlight the potential of talaporfin sodium as a clinically translatable radiosensitizer for RDT, offering a promising strategy for the treatment of deep-seated cancers such as pancreatic carcinoma.
Publisher
MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
Subject
/ Animals
/ Glioma
/ Humans
/ Mice
/ mono-L-aspartyl chlorin e6 (NPe6)
/ Pancreatic Neoplasms - drug therapy
/ Pancreatic Neoplasms - pathology
/ Pancreatic Neoplasms - radiotherapy
/ Photosensitizing Agents - pharmacology
/ Porphyrins - therapeutic use
/ Radiation-Sensitizing Agents - chemistry
/ Radiation-Sensitizing Agents - pharmacology
/ Radiation-Sensitizing Agents - therapeutic use
/ Reactive Oxygen Species - metabolism
/ RNA
/ Sodium
/ Tumors
/ X-Rays
