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<p>Photodynamic therapy (PDT) is known as a clinical treatment with significant potential for cancer therapy. However, the dilemma between therapeutic efficiency and hypoxic adaptability is a long-standing and unsolved issue in both type I and type II photosensitizers (PSs), significantly restricting their therapeutic use. Here, we report a generalizable “self-adaptive PDT” strategy, which has ensured efficient photodynamic action independent of normoxic and/or hypoxic tumor conditions. This strategy involves the insertion of an indazole building block into donor-π-acceptor (D-π-A) dyes, yielding a palette of type I/II switchable PSs that span visible and near-infrared range. These PSs are attached with the oxaliplatin (anticancer agent) to create hypoxia “self-adaptive PDT” probes, allowing to achieve highly cytotoxic effect in response to a range of oxygen concentrations (21%, 15%, 10%, 5%, to ⩽ 0.1%): In normoxic cells, the probe performs highly efficient type II PDT; in hypoxic cells, reduction triggers probe’s transformation from type II to I photosensitization, with the release of oxaliplatin for enhancing cytotoxicity. This <i>de novo</i> “self-adaptive PDT” strategy combines type II/I PDT-caused pyroptosis and oxaliplatin-induced immune cell death (ICD), synergistically contributing to cell death for constantly boosting therapeutic outcomes across normoxic to hypoxic tumor regions. As such, this strategy well resolves the trade-off effect between therapeutic efficiency and hypoxic adaptability in PDT.</p>

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Self-adaptive photodynamic therapy for boosting therapeutic efficiency in tumor

  • 期刊论文

  • 发表日期：

    2025年3月3日

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  • Xiaoqing Fu,
  • Yongkang Yao,
  • Qiang Liu,
  • Zhiqian Guo,
  • Chenxu Yan,
  • Wei-Hong Zhu

摘要

Photodynamic therapy (PDT) is known as a clinical treatment with significant potential for cancer therapy. However, the dilemma between therapeutic efficiency and hypoxic adaptability is a long-standing and unsolved issue in both type I and type II photosensitizers (PSs), significantly restricting their therapeutic use. Here, we report a generalizable “self-adaptive PDT” strategy, which has ensured efficient photodynamic action independent of normoxic and/or hypoxic tumor conditions. This strategy involves the insertion of an indazole building block into donor-π-acceptor (D-π-A) dyes, yielding a palette of type I/II switchable PSs that span visible and near-infrared range. These PSs are attached with the oxaliplatin (anticancer agent) to create hypoxia “self-adaptive PDT” probes, allowing to achieve highly cytotoxic effect in response to a range of oxygen concentrations (21%, 15%, 10%, 5%, to ⩽ 0.1%): In normoxic cells, the probe performs highly efficient type II PDT; in hypoxic cells, reduction triggers probe’s transformation from type II to I photosensitization, with the release of oxaliplatin for enhancing cytotoxicity. This de novo “self-adaptive PDT” strategy combines type II/I PDT-caused pyroptosis and oxaliplatin-induced immune cell death (ICD), synergistically contributing to cell death for constantly boosting therapeutic outcomes across normoxic to hypoxic tumor regions. As such, this strategy well resolves the trade-off effect between therapeutic efficiency and hypoxic adaptability in PDT.