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Bioorthogonal targeted cell membrane vesicles/cell-sheet composites reduce postoperative tumor recurrence and scar formation of melanoma
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-06-25 , DOI: 10.1016/j.jconrel.2024.06.038
Xinrui Yang , Zhanxue Xu , Fan Shu , Jiangwei Xiao , Yuqing Zeng , Xingyu Lu , Fei Yu , Lifang Xi , Fang Cheng , Botao Gao , Hongbo Chen

While surgical resection is the predominant clinical strategy in the treatment of melanoma, postoperative recurrence and undetectable metastasis are both pernicious drawbacks to this otherwise highly successful approach. Furthermore, the deep cavities result from tumor excision can leave long lasting wounds which are slow to heal and often leave visible scars. These unmet needs are addressed in the present work through the use of a multidimensional strategy, and also promotes wound healing and scar reduction. In the first phase, cell membrane-derived nanovesicles (NVs) are engineered to show PD-1 and dibenzocyclooctyne (DBCO). These are capable of reactivating T cells by blocking the PD-1/PD-L1 pathway. In the second phase, azido (N) labeled mesenchymal stem cells (MSCs) are cultured into cell sheets using tissue engineering, then apply directly to surgical wounds to enhance tissue repair. Owing to the complementary association between DBCO and N groups, PD-1 NVs were accumulated at the site of excision. This strategy can inhibit postoperative tumor recurrence and metastasis, whilst also promoting wound healing and reducing scar formation. The results of this study set a precedent for a new and innovative multidimensional therapeutic strategy in the postoperative treatment of melanoma.

中文翻译:


生物正交靶向细胞膜囊泡/细胞片复合材料减少术后肿瘤复发和黑色素瘤疤痕形成



虽然手术切除是治疗黑色素瘤的主要临床策略,但术后复发和无法检测到的转移都是这种非常成功的方法的致命缺点。此外,肿瘤切除产生的深腔可能会留下愈合缓慢且经常留下明显疤痕的持久伤口。这些未满足的需求在目前的工作中通过使用多维策略得到解决,并且还促进伤口愈合和疤痕减少。在第一阶段,细胞膜衍生的纳米囊泡 (NV) 被设计为显示 PD-1 和二苯并环辛炔 (DBCO)。它们能够通过阻断 PD-1/PD-L1 通路来重新激活 T 细胞。在第二阶段,使用组织工程将叠氮(N)标记的间充质干细胞(MSC)培养成细胞片,然后直接应用于手术伤口以增强组织修复。由于 DBCO 和 N 组之间的互补关联,PD-1 NV 在切除部位积累。该策略可以抑制术后肿瘤复发和转移,同时还可以促进伤口愈合并减少疤痕形成。这项研究的结果为黑色素瘤术后治疗的新型创新多维治疗策略开创了先例。
更新日期:2024-06-25
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