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<p>Controllable photoreaction transition of photosensitizers (PSs) provides a highly promising approach for achieving efficient photodynamic therapy (PDT). However, tumor microenvironment-triggered phototransition remains a significant challenge and has not yet been reported. In this work, we develop a hydrogen bond self-assembly (HBSA) strategy that is triggered by the acidic tumor microenvironment to enable the photodynamic transition of tetra(4-carboxylphenyl)porphyrin (TCPP) PSs from type II to type I reactions. Upon self-assembly of TCPP monomers into TCPP assemblies (TCPP-ass), the generated reactive oxygen species shift from singlet oxygen to superoxide anions, which induces caspase-3/GSDME-mediated programmed pyroptosis, enabling rapid and complete solid tumor elimination with minimized adverse effects and enhanced therapeutic efficacy. Crucially, the HBSA process occurs exclusively within tumor cells, and this tumor-specific self-assembly strategy not only utilizes high tissue penetration of TCPP molecular-PSs, but also avoids phototoxicity caused by the formation and accumulation of TCPP-ass nano-PSs in normal tissue, providing an innovative approach for precise cancer therapy.</p>

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Pursuing precise cancer therapy: tumor microenvironment-triggered hydrogen bond self-assembly enables photoreaction transition from type II to type I

  • 期刊论文

  • 发表日期：

    2025年8月27日

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  • Mingjie Ye,
  • Hanbin Xu,
  • Mengli Liu,
  • Mengqi Zhao,
  • Shilei Fan,
  • Mahmound Elsayed Hafez,
  • Binbin Chen,
  • Dawei Li

摘要

Controllable photoreaction transition of photosensitizers (PSs) provides a highly promising approach for achieving efficient photodynamic therapy (PDT). However, tumor microenvironment-triggered phototransition remains a significant challenge and has not yet been reported. In this work, we develop a hydrogen bond self-assembly (HBSA) strategy that is triggered by the acidic tumor microenvironment to enable the photodynamic transition of tetra(4-carboxylphenyl)porphyrin (TCPP) PSs from type II to type I reactions. Upon self-assembly of TCPP monomers into TCPP assemblies (TCPP-ass), the generated reactive oxygen species shift from singlet oxygen to superoxide anions, which induces caspase-3/GSDME-mediated programmed pyroptosis, enabling rapid and complete solid tumor elimination with minimized adverse effects and enhanced therapeutic efficacy. Crucially, the HBSA process occurs exclusively within tumor cells, and this tumor-specific self-assembly strategy not only utilizes high tissue penetration of TCPP molecular-PSs, but also avoids phototoxicity caused by the formation and accumulation of TCPP-ass nano-PSs in normal tissue, providing an innovative approach for precise cancer therapy.