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Background <p>Tumor biophysics is characterized by a fundamental aspect known as hypoxia. Melatonin (MLT) can decrease the activity of hypoxia-inducible factors (HIFs), thereby preventing tumor cell survival, proliferation, invasion, metastasis, angiogenesis, and energy metabolism.</p> Results <p>To monitor bioluminescence and assess the ability of combined MLT and photothermal therapy (PTT) to alleviate hypoxia, we constructed a modified A549-HRE-Luc cell line that responded to hypoxia. A versatile nanocarrier was developed to encapsulate MLT and combine near-infrared (NIR)-II fluorescence imaging, magnetic resonance (MR) imaging, and PTT, to effectively suppress tumor HIFs. The therapeutic effects of MLT on HIF-1α and PTT-mediated alleviation of tumor hypoxia were assessed via bioluminescence, which was contributed by the luciferase reporter gene in vivo. Additionally, it demonstrated the capability of NIR-II fluorescence imaging and T<sub>1</sub>-weighted MR imaging by including Mn<sup>2+</sup>, and the AS1411 aptamers, which were coordinated with metal ions, was used to specifically target the modified A549-HRE-Luc cells.</p> Conclusions <p>Ultimately, the findings from both in vitro and in vivo experiments demonstrated that the simultaneous use of MLT and PTT could effectively suppress hypoxia in tumors and trigger programmed apoptosis. As a result, this approach holds promise as a potential combined therapeutic option with enhanced therapeutic effects.</p> Graphical Abstract <p></p>

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In vivo dynamic monitoring of self-assembled melatonin nanodrug combined with photothermal effects to alleviate hypoxia to attenuate tumor aggressiveness

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Yun Zeng,
  • Dan Chen,
  • Ke Li,
  • Xueqing Kang,
  • Peng Chang,
  • Yijun Lu,
  • Jingwen Ma,
  • Wei Wang,
  • Qinglai Yang,
  • Li Tang,
  • Wenhua Zhan,
  • Qi Pan,
  • Yonghua Zhan

摘要

Background

Tumor biophysics is characterized by a fundamental aspect known as hypoxia. Melatonin (MLT) can decrease the activity of hypoxia-inducible factors (HIFs), thereby preventing tumor cell survival, proliferation, invasion, metastasis, angiogenesis, and energy metabolism.

Results

To monitor bioluminescence and assess the ability of combined MLT and photothermal therapy (PTT) to alleviate hypoxia, we constructed a modified A549-HRE-Luc cell line that responded to hypoxia. A versatile nanocarrier was developed to encapsulate MLT and combine near-infrared (NIR)-II fluorescence imaging, magnetic resonance (MR) imaging, and PTT, to effectively suppress tumor HIFs. The therapeutic effects of MLT on HIF-1α and PTT-mediated alleviation of tumor hypoxia were assessed via bioluminescence, which was contributed by the luciferase reporter gene in vivo. Additionally, it demonstrated the capability of NIR-II fluorescence imaging and T1-weighted MR imaging by including Mn2+, and the AS1411 aptamers, which were coordinated with metal ions, was used to specifically target the modified A549-HRE-Luc cells.

Conclusions

Ultimately, the findings from both in vitro and in vivo experiments demonstrated that the simultaneous use of MLT and PTT could effectively suppress hypoxia in tumors and trigger programmed apoptosis. As a result, this approach holds promise as a potential combined therapeutic option with enhanced therapeutic effects.

Graphical Abstract