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多功能金属有机框架外骨骼保护生物杂交精子微型机器人,用于从周围威胁中进行主动药物递送。

Multifunctional Metal-Organic Framework Exoskeletons Protect Biohybrid Sperm Microrobots for Active Drug Delivery from the Surrounding Threats.

作者信息

Chen Qiwei, Tang Songsong, Li Yangyang, Cong Zhaoqing, Lu Dongdong, Yang Qingxin, Zhang Xueji, Wu Song

机构信息

Teaching Center of Shenzhen Luohu Hospital, Shantou University Medical College, Shantou 515000, P. R. China.

Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2021 Dec 15;13(49):58382-58392. doi: 10.1021/acsami.1c18597. Epub 2021 Dec 3.

DOI:10.1021/acsami.1c18597
PMID:34860489
Abstract

Utilizing spermatozoa as the engine unit of robotic systems at a microscale has brought revolutionized inspirations and strategies to the biomedical community. However, the motility of sperms is impaired by the surrounding threats. For example, the antisperm antibody (AsA) can specifically bind with surface antigens on the sperm membrane and adversely affect their propulsion, hindering the operation of sperm-based microrobots in practical environments. In the present work, we report a biohybrid sperm microrobot by encapsulating sperm cells within metal-organic frameworks (MOFs) and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) (ZIFSpermbot), capable of active drug delivery and cytoprotection from the biological threats of AsA. ZIF-8 NPs can be facilely coated on the sperm membrane through complexation with tannic acid. Such cell surface engineering has a negligible impact on sperm motility under optimized conditions. The selective permeability of the resulting porous ZIF-8 wrappings protects ZIFSpermbots from the specific binding of AsA, enabling the preservation of intrinsic propulsion of the sperm engine. Besides, ZIF-8 wrappings sustainably release zinc ions and attenuate the oxidative damage generated in sperm cells, allowing the maintenance of sperm movement. Combining the effective protection of sperm propulsion with the drug-loading capacity of ZIF-8 NPs provides new applicability to ZIFSpermbots in risky surroundings with AsA, exhibiting rapid migration in a microfluidic device for active drug delivery with enhanced therapeutic efficacy due to their retained effective propulsion. Imparting bioengine-based microrobots with multifunctional wrappings holds great promise for designing adaptive cell robots that endure harsh environments toward locally extended and diverse operations, facilitating their use in practical and clinical applications.

摘要

在微观尺度上利用精子作为机器人系统的驱动单元,为生物医学领域带来了革命性的灵感和策略。然而,精子的运动能力会受到周围威胁的影响。例如,抗精子抗体(AsA)可以特异性地与精子膜上的表面抗原结合,对精子的推进产生不利影响,从而阻碍基于精子的微型机器人在实际环境中的运行。在本研究中,我们报道了一种生物杂交精子微型机器人,它通过将精子细胞包裹在金属有机框架(MOF)和沸石咪唑酯骨架-8(ZIF-8)纳米颗粒(ZIFSpermbot)中,能够实现主动药物递送并对AsA的生物威胁起到细胞保护作用。ZIF-8纳米颗粒可以通过与单宁酸络合轻松地包覆在精子膜上。在优化条件下,这种细胞表面工程对精子运动能力的影响可以忽略不计。所得多孔ZIF-8包裹层的选择性渗透性保护ZIFSpermbot免受AsA的特异性结合,从而保留精子发动机的固有推进能力。此外,ZIF-8包裹层可持续释放锌离子并减轻精子细胞中产生的氧化损伤,从而维持精子的运动。将对精子推进的有效保护与ZIF-8纳米颗粒的药物负载能力相结合,使得ZIFSpermbot在存在AsA的危险环境中具有新的适用性,由于其保留了有效的推进能力,在微流控装置中能够快速迁移以进行主动药物递送,从而提高治疗效果。为基于生物工程的微型机器人赋予多功能包裹层,对于设计能够在恶劣环境中持久运行以实现局部扩展和多样化操作的适应性细胞机器人具有巨大潜力,有助于它们在实际和临床应用中的使用。

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