A red blood cell-derived bionic microrobot capable of hierarchically adapting to five critical stages in systemic drug delivery

Ya-Xuan Zhu, Hao-Ran Jia, Yao-Wen Jiang, Yuxin Guo, Qiu-Yi Duan, Ke-Fei Xu, Bai-Hui Shan, Xiaoyang Liu, Xiaokai Chen, Fu-Gen Wu
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Abstract

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an “all-in-one” red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are “immolated” under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

Abstract Image

一种源自红细胞的仿生微型机器人,能够分层适应全身给药过程中的五个关键阶段
系统给药化学药物的肿瘤靶向效率在很大程度上决定了抗癌治疗的疗效。主要的挑战在于药物输送系统必须分层克服复杂多样的生物障碍,才能到达细胞/亚细胞靶点。在此,我们开发了一种由红细胞(RBC)衍生的 "一体化 "微机器人,它能分层适应全身给药过程中的五个关键阶段,即循环、蓄积、释放、外渗和渗透。由于微机器人的表面特性几乎完全相同,因此它们在血液循环中的表现与天然 RBC 类似,但可以通过磁力操纵在肿瘤等感兴趣的区域积聚。接下来,微机器人在激光照射下 "沉浸",以释放治疗货物,并通过产生热量,促进药物通过血管屏障外渗。作为一种胶质剂,吡非尼酮(PFD)可以抑制细胞外基质的形成,增加化学药物在实体瘤中的渗透深度。研究表明,该系统能有效抑制小鼠模型中的原发性和转移性肿瘤,且无明显副作用,可能代表了一种用于生物医学应用的新型智能仿生机器人。
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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CiteScore
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