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<p>The dual-responsive targeted photosensitizer (PS) exhibits significantly enhanced selectivity, enabling precise and safety in photodynamic therapy (PDT) for tumor treatment. However, synthetically endowing a single molecule with both targeting functionality and dual-responsive properties is an extremely complex task. Thus, research in this related field is relatively scarce. Herein, we present a novel PS named B-HCPP-RGD, which integrates α<sub>V</sub>β<sub>3</sub> integrin receptor targeting capabilities with dual responsiveness to both H<sub>2</sub>O<sub>2</sub> and cathepsin B. This PS can specifically recognize tumor cells and respond to the overexpressed H<sub>2</sub>O<sub>2</sub> and cathepsin B in tumor cells, ultimately releasing type I PS (HCEA) with a high reactive oxygen species (ROS) yield. <i>In vitro</i> studies demonstrated that B-HCPP-RGD exhibits minimal phototoxicity towards normal cells, while showing significant phototoxicity towards tumor cells. Even under hypoxic conditions, B-HCPP-RGD maintains strong phototoxicity towards tumor cells. <i>In vivo</i> studies revealed that B-HCPP-RGD can actively target the tumor and achieve a high tumor inhibition rate. This study establishes a novel approach to enhance the efficacy and precision of PDT for tumor treatment.</p>

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Dual-responsive peptide-photosensitizer conjugate based on hypocrellin derivative for tumor-targeted photodynamic therapy

  • 期刊论文

  • 发表日期：

    2025年10月10日

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  • Tong Mu,
  • Xiuli Zheng,
  • Yueke Yuan,
  • Yanping Wang,
  • Tian Liu,
  • Hongxue Li,
  • Jiasheng Wu,
  • Fan Li,
  • Wenjun Zhang,
  • Chun-Sing Lee,
  • Weimin Liu,
  • Pengfei Wang

摘要

The dual-responsive targeted photosensitizer (PS) exhibits significantly enhanced selectivity, enabling precise and safety in photodynamic therapy (PDT) for tumor treatment. However, synthetically endowing a single molecule with both targeting functionality and dual-responsive properties is an extremely complex task. Thus, research in this related field is relatively scarce. Herein, we present a novel PS named B-HCPP-RGD, which integrates αVβ3 integrin receptor targeting capabilities with dual responsiveness to both H2O2 and cathepsin B. This PS can specifically recognize tumor cells and respond to the overexpressed H2O2 and cathepsin B in tumor cells, ultimately releasing type I PS (HCEA) with a high reactive oxygen species (ROS) yield. In vitro studies demonstrated that B-HCPP-RGD exhibits minimal phototoxicity towards normal cells, while showing significant phototoxicity towards tumor cells. Even under hypoxic conditions, B-HCPP-RGD maintains strong phototoxicity towards tumor cells. In vivo studies revealed that B-HCPP-RGD can actively target the tumor and achieve a high tumor inhibition rate. This study establishes a novel approach to enhance the efficacy and precision of PDT for tumor treatment.