Ressnerova Alzbeta, Heger Zbynek, Pumera Martin
Central European Institute of Technology, Brno University of Technology, Purkynova 123, CZ-612 00, Brno, Czech Republic.
Research Group for Molecular Biology and Nanomedicine, Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00, Brno, Czech Republic.
Chem Soc Rev. 2025 Feb 17;54(4):1924-1956. doi: 10.1039/d4cs00483c.
In the dynamic realm of translational nanorobotics, the endeavor to develop nanorobots carrying therapeutics in rational applications necessitates a profound understanding of the biological landscape of the human body and its complexity. Within this landscape, biological membranes stand as critical barriers to the successful delivery of therapeutic cargo to the target site. Their crossing is not only a challenge for nanorobotics but also a pivotal criterion for the clinical success of therapeutic-carrying nanorobots. Nevertheless, despite their urgency, strategies for membrane crossing in translational nanorobotics remain relatively underrepresented in the scientific literature, signaling an opportunity for further research and innovation. This review focuses on nanorobots with various propulsion mechanisms from chemical and physical to hybrid mechanisms, and it identifies and describes four essential biological membranes that represent the barriers needed to be crossed in the therapeutic journey of nanorobots in applications. First is the entry point into the blood stream, which is the skin or mucosa or intravenous injection; next is the exit from the bloodstream across the endothelium to the target site; further is the entry to the cell through the plasma membrane and, finally, the escape from the lysosome, which otherwise destroys the cargo. The review also discusses design challenges inherent in translating nanorobot technologies to real-world applications and provides a critical overview of documented membrane crossings. The aim is to underscore the need for further interdisciplinary collaborations between chemists, materials scientists and chemical biologists in this vital domain of translational nanorobotics that has the potential to revolutionize the field of precision medicine.
在转化纳米机器人技术这个充满活力的领域中，开发能够在合理应用中携带治疗剂的纳米机器人，需要对人体的生物环境及其复杂性有深刻的理解。在这个环境中，生物膜是将治疗性负载成功递送至靶位点的关键障碍。跨越生物膜不仅是纳米机器人技术面临的一项挑战，也是携带治疗剂的纳米机器人临床成功的关键标准。然而，尽管其紧迫性，但转化纳米机器人技术中跨越膜的策略在科学文献中仍然相对较少被提及，这表明仍有进一步研究和创新的机会。本综述聚焦于具有从化学、物理到混合机制等各种推进机制的纳米机器人，并识别和描述了四种重要的生物膜，它们代表了纳米机器人在应用中的治疗过程中需要跨越的障碍。首先是进入血流的入口点，即皮肤、黏膜或静脉注射；其次是从血流穿过内皮细胞到达靶位点；再就是通过质膜进入细胞，最后是从溶酶体中逃脱，否则溶酶体会破坏负载。该综述还讨论了将纳米机器人技术转化为实际应用中固有的设计挑战，并对已记录的膜跨越情况进行了批判性概述。目的是强调在转化纳米机器人技术这一至关重要的领域中，化学家、材料科学家和化学生物学家之间进一步开展跨学科合作的必要性，该领域有可能彻底改变精准医学领域。
