Platelets loaded with alteplase exert fibrinolytic activity in human whole blood and plasma

IF 2.1 4区医学 Q2 HEMATOLOGY

Experimental hematology Pub Date : 2025-09-11 DOI:10.1016/j.exphem.2025.105248

Masataka Inoue , Masahiro Ohwada , Teruhiko Negishi , Nobuo Watanabe

引用次数: 0

Abstract

The utilization of alteplase for the management of intracerebral thromboembolism is associated with an elevated risk of intracerebral hemorrhage. To mitigate this risk, we investigated the fibrinolytic effect of alteplase-loaded platelets as a preliminary step in the development of a biocompatible drug delivery system (DDS). In this context, we demonstrated that platelet loaded with alteplase exhibited thrombolytic efficacy. Therefore, a drug DDS that employs alteplase-loaded platelets may offer a promising avenue for the development of a more biocompatible and less invasive thrombolytic therapy.

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满载阿替普酶的血小板在人全血和血浆中发挥纤溶活性。

阿替普酶用于脑血栓栓塞的治疗与脑出血的风险升高有关。为了降低这种风险，我们研究了载阿替酶血小板的纤溶作用，作为开发生物相容性给药系统（DDS）的初步步骤。在这种情况下，本研究的目的是确定阿替普酶是否可以装载到血小板上，确定阿替普酶装载的血小板的任何功能改变，并确定阿替普酶装载的血小板是否具有纤溶作用。将荧光阿替普酶与血小板孵育，观察并定量产生的荧光。在二磷酸腺苷（adenosine diphosphate， ADP）刺激下，血小板上CD62P的表达被量化为血小板活化的一个指标。此外，用阿替普酶处理的血小板在整个凝血过程中监测全血粘度和血浆吸光度的变化。因此，在血小板上观察到荧光标记的阿替普酶，表明它已经成功地装载到血小板上。此外，在ADP刺激后，满载阿替普酶的血小板表达CD62P。观察到细胞内阿替普酶浓度在ADP刺激下下降。满载阿替普酶的血小板在全血和血浆中显示纤溶活性。因此，使用阿替酶装载血小板的药物DDS可能为开发更具生物相容性和更少侵入性的溶栓治疗提供了一条有希望的途径。

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

Experimental hematology 医学-血液学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

58 days

期刊介绍： Experimental Hematology publishes new findings, methodologies, reviews and perspectives in all areas of hematology and immune cell formation on a monthly basis that may include Special Issues on particular topics of current interest. The overall goal is to report new insights into how normal blood cells are produced, how their production is normally regulated, mechanisms that contribute to hematological diseases and new approaches to their treatment. Specific topics may include relevant developmental and aging processes, stem cell biology, analyses of intrinsic and extrinsic regulatory mechanisms, in vitro behavior of primary cells, clonal tracking, molecular and omics analyses, metabolism, epigenetics, bioengineering approaches, studies in model organisms, novel clinical observations, transplantation biology and new therapeutic avenues.