红细胞衍生囊泡作为阿霉素的系统递送系统，用于改善溶酶体-线粒体轴的癌症治疗。
RBC-derived vesicles as a systemic delivery system of doxorubicin for lysosomal-mitochondrial axis-improved cancer therapy.
机构信息
Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan.
Department of Laboratory Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei 100225, Taiwan.
出版信息
J Adv Res. 2020 Nov 24;30:185-196. doi: 10.1016/j.jare.2020.11.009. eCollection 2021 May.
INTRODUCTION
Chemotherapeutic drugs are the main intervention for cancer management, but many drawbacks impede their clinical applications. Nanoparticles as drug delivery systems (DDSs) offer much promise to solve these limitations.
OBJECTIVES
A novel nanocarrier composed of red blood cell (RBC)-derived vesicles (RDVs) surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs was investigated for improved cancer therapy.
METHODS
We investigated the antineoplastic performance of Dox-gluRDVs through intravenous () administration in the mouse model bearing subcutaneous () B16F10 tumor and examined the antitumor mechanism and efficacy in a panel of cancer cell lines.
RESULTS
Dox-gluRDVs can exert superior anticancer activity than free Dox and . Distinct from free Dox that is mainly located in the nucleus, but instead Dox-gluRDVs release and efficiently deliver the majority of their conjugated Dox into lysosomes. In vitro mechanism study reveals the critical role of lysosomal Dox accumulation-mediated mitochondrial ROS overproduction followed by the mitochondrial membrane potential loss and the activation of apoptotic signaling for superior anticancer activity of Dox-gluRDVs.
CONCLUSION
This work demonstrates the great potential of RDVs to serve a biological DDS of Dox for systemic administration to improve conventional cancer chemotherapeutics.
简介
化疗药物是癌症治疗的主要干预手段，但许多缺点阻碍了它们的临床应用。纳米颗粒作为药物递送系统（DDS）为解决这些限制提供了很大的希望。
目的
使用戊二醛（glu）将阿霉素（Dox）表面连接到红细胞（RBC）衍生的囊泡（RDV）上，形成 Dox-gluRDV，用于改善癌症治疗，我们研究了这种新型纳米载体。
方法
我们通过静脉内（）给予携带皮下（）B16F10 肿瘤的小鼠模型，研究了 Dox-gluRDV 的抗肿瘤性能，并在一系列癌细胞系中研究了其抗肿瘤机制和疗效。
结果
Dox-gluRDV 可以比游离 Dox 和发挥更好的抗癌活性。与主要位于细胞核内的游离 Dox 不同，Dox-gluRDV 释放并有效地将其大部分共轭 Dox 递送至溶酶体。体外机制研究表明，溶酶体 Dox 积累介导的线粒体 ROS 过度产生，随后线粒体膜电位丧失和凋亡信号激活，是 Dox-gluRDV 具有优异抗癌活性的关键。
结论
这项工作证明了 RDV 作为 Dox 的生物 DDS 用于系统给药以改善常规癌症化疗的巨大潜力。
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