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一种具有高载药量和pH敏感药物释放特性的基于硅藻的生物杂交微型机器人用于靶向治疗。

A diatom-based biohybrid microrobot with a high drug-loading capacity and pH-sensitive drug release for target therapy.

作者信息

Li Mengyue, Wu Junfeng, Lin Daojing, Yang Jia, Jiao Niandong, Wang Yuechao, Liu Lianqing

机构信息

State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China; Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang 110016, China; University of Chinese Academy of Sciences, Beijing 100049, China.

State Key Laboratory of Robotics, Shenyang Institute of Automation, Chinese Academy of Sciences, Shenyang 110016, China; Institutes for Robotics and Intelligent Manufacturing, Chinese Academy of Sciences, Shenyang 110016, China.

出版信息

Acta Biomater. 2022 Dec;154:443-453. doi: 10.1016/j.actbio.2022.10.019. Epub 2022 Oct 13.

Abstract

Targeted delivery is a promising mean for various biomedical applications, and various micro/nano robots have been created for drug delivery. Mesoporous silica has been shown to be successful as a drug delivery carrier in numerous studies. However, mesoporous silica preparation usually requires expensive and toxic chemicals, which limits its biomedical applications. Diatoms, as the naturally porous silica structure, are promising substitutes for the artificial mesoporous silica preparation. However, the current studies utilizing intact diatom frustules as drug delivery packets lack flexible and controllable locomotion. Herein, we propose a biohybrid magnetic microrobot based on Thalassiosira weissflogii frustules (TWFs) as a cargo packet for targeted drug delivery using a simple preparation method. Biohybrid microrobots are fabricated in large quantities by attaching magnetic nanoparticles (FeO) to the surface of diatoms via electrostatic adsorption. Biohybrid microrobots are agile and controllable under the influence of external magnetic fields. They could be precisely controlled to follow specific trajectories or to move as swarms. The cooperation of the two motion modes of the biohybrid microrobots increased microrobots' environmental adaptability. Microrobots have a high drug-loading capacity and pH-sensitive drug release. In vitro cancer cell experiments further demonstrated the controllability of diatom microrobots for targeted drug delivery. The biohybrid microrobots reported in this paper convert natural diatoms into cargo packets for biomedical applications, which possess active and controllable properties and show huge potential for targeted anticancer therapy. STATEMENT OF SIGNIFICANCE: In this study, diatoms with good biocompatibility were used to prepare biohybrid magnetic microrobots. Compared with the current diatom-based systems for drug delivery, the microrobots prepared in this study for targeted drug delivery have more flexible motion characteristics and exhibit certain swarming behaviors. Under the same magnetic field strength, by changing the magnetic field frequency, the movement state of the diatoms can be changed to pass through the narrow channel, so that it has better environmental adaptability.

摘要

靶向递送是各种生物医学应用中一种很有前景的手段,人们已经制造出各种微纳机器人用于药物递送。在众多研究中,介孔二氧化硅已被证明是一种成功的药物递送载体。然而,介孔二氧化硅的制备通常需要昂贵且有毒的化学物质,这限制了其在生物医学领域的应用。硅藻作为天然的多孔二氧化硅结构,有望成为人工介孔二氧化硅制备的替代品。然而,目前利用完整硅藻壳作为药物递送包的研究缺乏灵活可控的运动能力。在此,我们提出一种基于威氏海链藻壳(TWFs)的生物杂交磁性微机器人,作为一种货物包,采用简单的制备方法用于靶向药物递送。通过静电吸附将磁性纳米颗粒(FeO)附着在硅藻表面,大量制备生物杂交微机器人。生物杂交微机器人在外部磁场的影响下灵活且可控。它们可以被精确控制以遵循特定轨迹或成群移动。生物杂交微机器人这两种运动模式的协同作用提高了微机器人的环境适应性。微机器人具有高载药能力和pH敏感的药物释放特性。体外癌细胞实验进一步证明了硅藻微机器人用于靶向药物递送的可控性。本文报道的生物杂交微机器人将天然硅藻转化为用于生物医学应用的货物包,具有主动和可控的特性,在靶向抗癌治疗中显示出巨大潜力。重要意义声明:在本研究中,利用具有良好生物相容性的硅藻制备生物杂交磁性微机器人。与目前基于硅藻的药物递送系统相比,本研究制备的用于靶向药物递送的微机器人具有更灵活的运动特性,并表现出一定的群体行为。在相同磁场强度下,通过改变磁场频率,可以改变硅藻的运动状态以穿过狭窄通道,从而使其具有更好的环境适应性。

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