Multifunctional Metal-Organic Framework Exoskeletons Protect Biohybrid Sperm Microrobots for Active Drug Delivery from the Surrounding Threats
Multifunctional Metal-Organic Framework Exoskeletons Protect Biohybrid Sperm Microrobots for Active Drug Delivery from the Surrounding Threats
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DOI：
10.1021/acsami.1c18597
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发表时间：
2021-12-15
影响因子：
9.5
通讯作者：
Wu, Song
中科院分区：
文献类型：
--
作者：
Chen, Qiwei;Tang, Songsong;Wu, Song
将精子用作微型机器人系统的动力单元为生物医学界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损害。例如，抗精子抗体（AsA）能够与精子膜表面的抗原特异性结合，对其推进力产生不利影响，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混合精子微型机器人，它是通过将精子细胞包裹在金属 - 有机框架（MOFs）和沸石咪唑酯骨架 - 8（ZIF - 8）纳米颗粒（NPs）中制成的（ZIFSpermbot），能够实现主动药物递送，并能保护细胞免受AsA的生物威胁。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。由此产生的多孔ZIF - 8包裹层的选择性渗透性保护ZIFSpermbots免受AsA的特异性结合，从而能够保持精子引擎的固有推进力。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。将对精子推进力的有效保护与ZIF - 8纳米颗粒的载药能力相结合，为ZIFSpermbots在存在AsA的危险环境中提供了新的适用性，使其在微流控装置中能够快速迁移以实现主动药物递送，并且由于其保留了有效的推进力而提高了治疗效果。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适应恶劣环境以实现局部扩展和多样化操作的自适应细胞机器人具有很大的前景，有助于它们在实际和临床应用中的使用。
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.