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other·preclinical research, biomedical research, oncology, dermatology·PMC10821930

In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing

Nature Communications · 8 authors, 2 centres

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TL;DR

Researchers developed an in-situ-sprayed hydrogel (HIL@Z/P/H) combining a NIR-activated nanodrug with photosynthetic cyanobacteria (PCC 7942) to simultaneously prevent postsurgical melanoma recurrence/metastasis and promote wound healing in mouse models. The system achieved this through PDT-induced redox disruption, NO-mediated nitrosative stress, and long-lasting oxygen self-supply that reversed tumor and wound hypoxia.

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Under NIR laser, the nanodrug disrupted cellular redox homeostasis through simultaneous ROS generation and GSH depletion, while supplemented oxygen potentiated PDT-induced nitrosative stress and blocked HIF-1α signaling to inhibit metastasis. The photosynthetic oxygen and PCC 7942-secreted EVs synergistically promoted angiogenesis and wound healing. The study demonstrated dual functionality: prevention of tumor recurrence/metastasis and acceleration of wound healing.

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preclinical research

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ORIGINAL PAPER

PMC10821930

In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing

Nature Communications

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ABSTRACT

Abstract Surgery is the mainstay of treatment modality for malignant melanoma. However, the deteriorative hypoxic microenvironment after surgery is recognized as a stemming cause for tumor recurrence/metastasis and delayed wound healing. Here we design and construct a sprayable therapeutic hydrogel (HIL@Z/P/H) encapsulating tumor-targeted nanodrug and photosynthetic cyanobacteria (PCC 7942) to prevent tumor recurrence/metastasis while promote wound healing. In a postsurgical B16F10 melanoma model in female mice, the nanodrug can disrupt cellular redox homeostasis via the photodynamic therapy-induced cascade reactions within tumor cells. Besides, the photosynthetically generated O 2 by PCC 7942 can not only potentiate the oxidative stress-triggered cell death to prevent local recurrence of residual tumor cells, but also block the signaling pathway of hypoxia-inducible factor 1α to inhibit their distant metastasis. Furthermore, the long-lasting O 2 supply and PCC 7942-secreted extracellular vesicles can jointly promote angiogenesis and accelerate the wound healing process. Taken together, the developed HIL@Z/P/H capable of preventing tumor recurrence/metastasis while promoting wound healing shows great application potential for postsurgical cancer therapy. Subject terms: Melanoma, Targeted therapies, Biomedical materials

CITATION EXPORT

Shuiling Chen, Yang Luo, Yang He et al.. In-situ-sprayed therapeutic hydrogel for oxygen-actuated Janus regulation of postsurgical tumor recurrence/metastasis and wound healing. Nature Communications. (2024). https://doi.org/10.1038/s41467-024-45072-x

AUTHORS

8 · 2 CENTRES

Shuiling Chen, Yang Luo, Yang He, Ming Li, Yongjian Liu, Xishen Zhou, Jianwen Hou, Shaobing Zhou

1Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031 China
2Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031 China