An artificial-enzyme-equipped immunoregulator blocks platelet-mediated breast cancer hematogenous metastasis

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2025-04-29 DOI:10.1016/j.biomaterials.2025.123380

Ben Hu , Huimin Lin , Xiaolong Quan , Fushan Sun , Fengling Zhang , Fang Zhang , Yu Wang , Yunhua Chang , Jigang Wang , Xiaohui Duan , Meng Yu

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引用次数: 0

Abstract

Platelet activation and adhesion on the surface of circulating tumor cells (CTCs) assist them in surviving within the vasculature and acquiring enhanced migratory potential. Simultaneously, protected by surrounding/covering "micro-thrombi," CTCs evade immune surveillance in circulation, thereby promoting hematogenous tumor metastasis. Based on this, we designed a self-assembling nanoenzyme drug GSNO@B (NO donor-modified GOx self-assembled with the hydrophobic drug BMS-202) against platelet-mediated tumor metastasis. This strategy involves the depletion of glucose by GOx, which inhibits platelets activity and reduces forming the micro-aggregation. Concurrently, the nanoenzyme in situ releases NO further diminishes the protective adhesion and micro-aggregation of platelet on the tumor cells surface, thereby exposing them in shear forces and immune recognition in the circulatory system. Concurrently, the disintegration of the nanoenzyme GSNO@B releases the immune checkpoint inhibitor BMS-202, further facilitating the immune clearance of CTCs. Therefore, through a three-step strategy, GSNO@B effectively suppresses primary tumors growth and metastatic tumors formation by blocking the platelet-mediated hematogenous tumor metastasis pathway.

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一种配备人工酶的免疫调节剂阻断血小板介导的乳腺癌血液转移

循环肿瘤细胞（CTCs）表面的血小板活化和粘附有助于它们在脉管系统内存活并获得增强的迁移潜力。同时，在周围/覆盖的“微血栓”的保护下，ctc逃避循环中的免疫监视，从而促进血液肿瘤转移。基于此，我们设计了一种抗血小板介导的肿瘤转移的自组装纳米酶药物GSNO@B （NO供体修饰的GOx与疏水药物BMS-202自组装）。这种策略涉及到GOx消耗葡萄糖，从而抑制血小板活性并减少微聚集的形成。同时，纳米酶在原位释放NO，进一步降低肿瘤细胞表面血小板的保护性粘附和微聚集，从而使肿瘤细胞暴露在剪切力和循环系统的免疫识别中。同时，纳米酶GSNO@B的分解释放免疫检查点抑制剂BMS-202，进一步促进ctc的免疫清除。因此，GSNO@B通过三步走的策略，通过阻断血小板介导的血液肿瘤转移途径，有效抑制原发肿瘤的生长和转移性肿瘤的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.