Chen Shuiling, Luo Yang, He Yang, Li Ming, Liu Yongjian, Zhou Xishen, Hou Jianwen, Zhou Shaobing
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China.
Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China.
Nat Commun. 2024 Jan 27;15(1):814. doi: 10.1038/s41467-024-45072-x.
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 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 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.
手术是恶性黑色素瘤治疗方式的主要手段。然而，术后恶化的缺氧微环境被认为是肿瘤复发/转移以及伤口愈合延迟的根源。在此，我们设计并构建了一种可喷涂的治疗性水凝胶（HIL@Z/P/H），其包裹着肿瘤靶向纳米药物和光合蓝细菌（PCC 7942），以预防肿瘤复发/转移，同时促进伤口愈合。在雌性小鼠的术后B16F10黑色素瘤模型中，纳米药物可通过肿瘤细胞内光动力疗法诱导的级联反应破坏细胞氧化还原稳态。此外，PCC 7942光合作用产生的氧气不仅可增强氧化应激引发的细胞死亡以防止残留肿瘤细胞局部复发，还能阻断缺氧诱导因子1α的信号通路以抑制其远处转移。此外，持续的氧气供应和PCC 7942分泌的细胞外囊泡可共同促进血管生成并加速伤口愈合过程。综上所述，所开发的HIL@Z/P/H能够预防肿瘤复发/转移，同时促进伤口愈合，在术后癌症治疗中显示出巨大的应用潜力。
