当前位置: X-MOL 学术Matter › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
T cell-mimicking platelet-drug conjugates
Matter ( IF 18.9 ) Pub Date : 2023-05-19 , DOI: 10.1016/j.matt.2023.04.026
Yinxian Yang, Yanfang Wang, Yuejun Yao, Shenqiang Wang, Yuqi Zhang, Gianpietro Dotti, Jicheng Yu, Zhen Gu

Cancer metastasis is the leading cause of cancer-related deaths. The indispensable role of platelets in tumor metastasis inspires the targeted delivery strategy by using platelet-drug conjugates (PDCs). Here, we armed platelets with granzyme B and perforin nanocomplexes to suppress cancer metastasis by leveraging the natural cytotoxic mechanism of T cells. Upon systemic administration, PDCs naturally capture circulating tumor cells (CTCs) and actively target nascent metastatic lesions, thus enhancing the targeted delivery efficiency. Subsequently, PDCs activated in situ by tumor cells can produce platelet microparticles (PMPs) that can actively target tumor cells by the expression of adhesion molecules such as P-selectin and thrombospondin-1 (TSP-1) and by secreting cytotoxic protein complexes mimicking cytotoxic lymphocytes. We demonstrated that the PDCs significantly suppressed lung metastasis in two tumor models, B16F10 melanomas and 4T1 breast carcinomas.



中文翻译:

模拟 T 细胞的血小板药物缀合物

癌症转移是癌症相关死亡的主要原因。血小板在肿瘤转移中不可或缺的作用激发了使用血小板药物缀合物(PDC)的靶向递送策略。在这里,我们用颗粒酶 B 和穿孔素纳米复合物武装血小板,通过利用 T 细胞的天然细胞毒性机制来抑制癌症转移。全身给药后,PDC 自然捕获循环肿瘤细胞 (CTC) 并主动靶向新生转移病灶,从而提高靶向递送效率。随后,PDCs原位激活肿瘤细胞产生的血小板微粒 (PMP) 可以通过表达 P-选择素和血小板反应蛋白-1 (TSP-1) 等粘附分子以及通过分泌模仿细胞毒性淋巴细胞的细胞毒性蛋白复合物来主动靶向肿瘤细胞。我们证明 PDC 在两种肿瘤模型(B16F10 黑色素瘤和 4T1 乳腺癌)中显着抑制肺转移。

更新日期:2023-05-19
down
wechat
bug