Baltaci Saadet Fatma, Akolpoglu Mukrime Birgul, Kalita Irina, Sourjik Victor, Sitti Metin
Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569, Stuttgart, Germany.
Stuttgart Center for Simulation Science (SC SimTech), University of Stuttgart, 70569, Stuttgart, Germany.
Adv Sci (Weinh). 2025 Jun 27:e05538. doi: 10.1002/advs.202505538.
Bacterial biohybrid microrobots possess significant potential for targeted cargo delivery and minimally invasive therapy. However, many challenges, such as biocompatibility, stability, and effective cargo loading, remain. Bacterial membrane vesicles, also referred to as minicells, offer a promising alternative for creating sub-micron scale biohybrid swimmers (minicell biohybrids) due to their active metabolism, non-dividing nature, robust structure, and high cargo-carrying capacity. Here, a biohybrid system is reported that utilizes motile minicells, ≈400 nm in diameter, generated by aberrant cell division of engineered Escherichia coli (E. coli), for the first time. Achieving over 99% purification from their parental bacterial cells, minicells are functionalized with magnetic nanoparticles (MNPs) to enable external magnetic control. Minicell biohybrids are capable of swimming at an average speed of up to 13.3 µm s and being steered under a uniform magnetic field of 26 mT. Furthermore, they exhibit a significantly high drug loading capacity (2.8 µg mL) while maintaining their motility and show pH-sensitive release of anticancer drug doxorubicin hydrochloride (DOX) under acidic conditions. Additionally, drug-loaded minicell biohybrids notably reduce the viability of SK-BR-3 breast cancer cells in vitro. This study introduces minicell biohybrids and establishes their potential as magnetically guided, drug-loaded biohybrid systems for targeted therapies in future medical applications.
细菌生物杂交微型机器人在靶向货物递送和微创治疗方面具有巨大潜力。然而,仍存在许多挑战,如生物相容性、稳定性和有效的货物装载等。细菌膜囊泡,也称为微细胞,由于其活跃的代谢、非分裂性质、坚固的结构和高载物能力,为创建亚微米级生物杂交游泳体(微细胞生物杂交体)提供了一种有前景的替代方案。在此,首次报道了一种生物杂交系统,该系统利用由工程化大肠杆菌(E. coli)异常细胞分裂产生的直径约400 nm的运动性微细胞。微细胞从其亲代细菌细胞中纯化率超过99%,并用磁性纳米颗粒(MNPs)进行功能化,以实现外部磁控。微细胞生物杂交体能以高达13.3 µm s的平均速度游动,并在26 mT的均匀磁场下被引导。此外,它们在保持运动性的同时表现出显著的高载药能力(2.8 µg mL),并在酸性条件下显示出抗癌药物盐酸阿霉素(DOX)的pH敏感释放。此外,载药微细胞生物杂交体在体外显著降低了SK-BR-3乳腺癌细胞的活力。这项研究引入了微细胞生物杂交体,并确立了它们作为未来医学应用中用于靶向治疗的磁导向、载药生物杂交系统的潜力。
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