纳米机器人在靶向药物递送系统中的研究进展

Progress on nanorobots for targeted drug delivery systems

纳米机器人技术在靶向药物递送领域的应用是纳米科学、生物医学、机械工程、力学、电子工程、信息与通信等多学科交叉融合的产物.由于体积小、可自主运动和精确操控,纳米机器人在精准治疗和纳米诊断等生物医学领域展示出巨大的发展潜力.本文从认识纳米机器人技术及靶向药物递送应用需求出发,简单回顾了靶向药物递送技术的发展历程,结合纳米机器人的类型、制造方式以及驱动方式,综述了国内外在靶向药物递送应用领域纳米机器人的研究进展.最后,梳理了纳米机器人在靶向药物递送应用研究中的重点方向,为我国未来的纳米机器人技术研究提供参考.

Nanorobots are artificial intelligence systems that simulate the construction of biological nanomachines and important biological events in the life process. They move autonomously in the biological medium by taking advantage of various forms of energy around and interacting with cells or tissues. They are nanomachines with sizes ranging from 1 to 100 nm.The nanorobots targeting drug delivery systems are a multi-interdisciplinary subject intersected by nano-science,biomedicine, and mechanical engineering. Due to their small size, autonomous movement, and precise control, nanorobots show great potential in biomedical fields such as precision therapy and nano-diagnosis. Nanorobots of small size are capable of moving into the deep area of the narrow-body tissues. Different from the nanodrugs delivered through the blood circulation system passively, nanorobots show their advantages in the autonomous movement towards targeted cells or tissues in various bio-mediums by being propelled by surrounding chemical/biochemical energy, external fields, or motile cells/microorganisms. Nanorobots research on targeted drug delivery aims to deliver the drug to the pathogen cells without affecting healthy cells, which improves drug efficacy and minimizes side effects. The study of nanorobots is a pioneering research field and their application in targeted drug delivery is supposed to promote the development of clinical medicine.In this review, we first retrospect the development of nanorobots for targeted drug delivery systems. Three key technological stages that promote the development of targeted drug delivery from the proposed concept to the demonstration are introduced. They are PEGylation, enhanced permeation and retention effect, and nanorobots technology.We then classify nanorobots into the following three types based on their materials, which are cell/microorganism type,artificial material type, and their combinations. Various fabrication methods of nanorobots that follow the bottom-up and top-down design principles are also presented in the classification part. The sustainable and reliable propulsion of nanorobots is an essential prerequisite for successful targeted drug delivery in a biological environment. The common power sources can be divided into chemical/biochemical energy, exogenous energy(magnetic fields, electric field, light,and ultra-sound), and bioenergy from motile cells or microorganisms. We review recent progress regarding nanorobots propelled by different energy and their application in vitro and in vivo targeted drug delivery. The mechanisms, merits, and limitations of each propulsion are also discussed in this part. At the end of the review, the key research challenges and directions of nanorobots are given. In order to meet the practical needs of biomedical applications, nanorobots still face many challenges in biosafety, actuation, in vivo navigation, in vivo safety, and other aspects. Considerable studies are based on in vitro experiments and in vivo experiments of animals. Due to the limitations of current biological imaging technologies and location tracking technologies, it is difficult to achieve precise control and positioning of nanorobots deep into human organs and tissues. Particular emphasis should be placed on the evaluation of biological safety, autonomous navigation, and precise manipulation in the complex bio-environment, visualization, and tracking of nanorobots. It should be noted that current research of nanorobots in targeted drug delivery is still in its infancy, it needs rigorous verification before the realization of nanorobots in human bodies.