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<p>Malignant melanoma of the skin is prone to metastasis and recurrence. Photodynamic therapy (PDT) excited by near-infrared (NIR) light, as a non-invasive method, is very suitable for treating malignant melanoma of the skin. However, because of the high expression of melanin that absorbs red or NIR light and consumes reactive oxygen species in malignant melanoma, achieving good PDT efficiency remains a challenge. In this study, we report a prodrug <b>SW-111</b> with a simple structure that can be activated by HOCl and ONOO<sup>−</sup>, and simultaneously release the photosensitizer methylene blue (MB) for PDT and the inhibitor 4-hydroxybenzaldehyde (4-HBA) that can inhibit tyrosinase activity and reduce melanin expression to enhance the PDT effect. <b>SW-111</b> can not only reduce melanin production in B16F10 cells but also exhibits excellent anti-tumor effects in a melanoma mouse model. The tumors are significantly suppressed at an inhibition rate of 98.8% according to the excised tumor weights at the end of the treatment and no recurrence happens after the mice are treated with both <b>SW-111</b> and laser.</p>

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One shot, twice the impact: synergistic reactive oxygen species-activated prodrug and tyrosinase inhibition for enhanced melanoma photodynamic therapy

  • 期刊论文

  • 发表日期：

    2025年7月4日

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  • Mengfan Zhang,
  • Lingyan Liu,
  • Peng Wei,
  • Wei Feng,
  • Tao Yi

摘要

Malignant melanoma of the skin is prone to metastasis and recurrence. Photodynamic therapy (PDT) excited by near-infrared (NIR) light, as a non-invasive method, is very suitable for treating malignant melanoma of the skin. However, because of the high expression of melanin that absorbs red or NIR light and consumes reactive oxygen species in malignant melanoma, achieving good PDT efficiency remains a challenge. In this study, we report a prodrug SW-111 with a simple structure that can be activated by HOCl and ONOO−, and simultaneously release the photosensitizer methylene blue (MB) for PDT and the inhibitor 4-hydroxybenzaldehyde (4-HBA) that can inhibit tyrosinase activity and reduce melanin expression to enhance the PDT effect. SW-111 can not only reduce melanin production in B16F10 cells but also exhibits excellent anti-tumor effects in a melanoma mouse model. The tumors are significantly suppressed at an inhibition rate of 98.8% according to the excised tumor weights at the end of the treatment and no recurrence happens after the mice are treated with both SW-111 and laser.