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<p>Photothermal therapy (PTT) is a non-invasive and highly selective tumor treatment. However, it triggers an inflammatory reaction and other adverse effects, including damage to the surrounding healthy tissue and an increased risk of tumor proliferation and metastasis. The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays a crucial role in regulating tumor development. In this study, we revealed that PTT activates the COX-2/PGE2 pathway. To mitigate the PTT-induced inflammation, based on polydopamine (PDA) and HS-β-cyclodextrin (HS-β-CD), we constructed a photothermal/anti-inflammatory nanoparticle system (named ICG@PDA-β-CD/CEL) loaded with the anti-inflammatory drug celecoxib (CEL) and the photosensitizer indocyanine green (ICG), which targets COX-2. This system helps PTT by (1) reducing proinflammatory molecules such as PGE2, tumor necrosis factor-α, and interleukin-6 and inhibiting the COX-2 and nuclear factor kappa-B signaling pathways, (2) suppressing vascular endothelial growth factor production to inhibit tumor angiogenesis, and (3) preventing tumor cell migration and invasion. Further results indicated that ICG@PDA-β-CD/CEL significantly curtailed tumor cell invasion and migration in vitro and suppressed the COX-2/PGE2 pathway in vivo, thereby markedly inhibiting both orthotopic tumor growth and metastasis. ICG@PDA-β-CD/CEL exhibits potent antitumor effects through its combined anti-inflammatory and photothermal therapies, providing a promising strategy for alleviating PTT-related adverse effects.</p>

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Targeting cyclooxygenase-2 using photothermal-anti-inflammatory nanoparticles to inhibit tumor growth and metastasis

  • 期刊论文

  • 发表日期：

    2025年9月19日

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  • Jiahui Cai,
  • Zutong Cui,
  • Wenming Liang,
  • Jianming Sun,
  • Zihan Zhang,
  • Shasha Zhao,
  • Zhiwei Liu,
  • Xiaoling Li,
  • Jian Li

摘要

Photothermal therapy (PTT) is a non-invasive and highly selective tumor treatment. However, it triggers an inflammatory reaction and other adverse effects, including damage to the surrounding healthy tissue and an increased risk of tumor proliferation and metastasis. The cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway plays a crucial role in regulating tumor development. In this study, we revealed that PTT activates the COX-2/PGE2 pathway. To mitigate the PTT-induced inflammation, based on polydopamine (PDA) and HS-β-cyclodextrin (HS-β-CD), we constructed a photothermal/anti-inflammatory nanoparticle system (named ICG@PDA-β-CD/CEL) loaded with the anti-inflammatory drug celecoxib (CEL) and the photosensitizer indocyanine green (ICG), which targets COX-2. This system helps PTT by (1) reducing proinflammatory molecules such as PGE2, tumor necrosis factor-α, and interleukin-6 and inhibiting the COX-2 and nuclear factor kappa-B signaling pathways, (2) suppressing vascular endothelial growth factor production to inhibit tumor angiogenesis, and (3) preventing tumor cell migration and invasion. Further results indicated that ICG@PDA-β-CD/CEL significantly curtailed tumor cell invasion and migration in vitro and suppressed the COX-2/PGE2 pathway in vivo, thereby markedly inhibiting both orthotopic tumor growth and metastasis. ICG@PDA-β-CD/CEL exhibits potent antitumor effects through its combined anti-inflammatory and photothermal therapies, providing a promising strategy for alleviating PTT-related adverse effects.