Platelet-Drug Conjugates Engineered via One-step Fusion Approach for Metastatic and Postoperative Cancer Treatment

IF 16.1 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Zhengjie Zhao, Yinxian Yang, Tao Sheng, Yuhang Bao, Ruixi Yu, Xinmin Yu, Shuangxu Jia, Qing Wu, Chaojie Zhu, Xinyuan Shen, Wentao Zhang, Ziyi Lu, Kangfan Ji, Xiaofeng Chen, Xinyun Jiang, Prof. Yuqi Zhang, Prof. Zhen Gu, Prof. Jicheng Yu
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Abstract

The exploration of cell-based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one-step fusion process. We demonstrate doxorubicin (DOX)-encapsulated liposomes conjugated with interleukin-15 (IL-15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models.

Abstract Image

通过一步融合法设计的血小板-药物共轭物用于癌症转移和术后治疗
以细胞为基础的癌症治疗药物递送系统的探索日益受到关注。如何在保持治疗细胞固有生物特性的前提下,以有效、安全、精确的方式设计出能负载多种药物的治疗细胞,仍然是人们十分关心的问题。在这里,我们报告了一种在一步融合过程中同时将多种药物载入血小板的策略。我们证明了与白细胞介素-15(IL-15)共轭的多柔比星(DOX)包裹脂质体能与血小板融合,在几分钟内实现细胞质药物负载和表面细胞因子修饰,负载效率超过 70%。由于其对转移性癌症和术后出血部位的固有靶向能力,工程血小板在小鼠 B16F10 黑色素瘤模型中显示出抑制肺转移和术后复发的协同治疗效果。
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来源期刊
CiteScore
26.60
自引率
6.60%
发文量
3549
审稿时长
1.5 months
期刊介绍: Angewandte Chemie, a journal of the German Chemical Society (GDCh), maintains a leading position among scholarly journals in general chemistry with an impressive Impact Factor of 16.6 (2022 Journal Citation Reports, Clarivate, 2023). Published weekly in a reader-friendly format, it features new articles almost every day. Established in 1887, Angewandte Chemie is a prominent chemistry journal, offering a dynamic blend of Review-type articles, Highlights, Communications, and Research Articles on a weekly basis, making it unique in the field.
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