人造细菌鞭毛基于DPPC脂质体的表面功能化研究

Remotely controlled medical microrobots have the potential to revolutionize minimally invasive medical tasks, such as targeted diagnosis and therapy. Among various approaches for powering microrobots, magnetic field actuation is promising for in vivo applications, because weak-strength magnetic fields are harmless to living cells and biological tissue. Artificial bacterial flagella (ABF) are magnetic-field-driven helical microrobots, which mimic the corkscrew propulsion strategy and are of comparable size to real bacterial such as E. coli. Previous work proposed flagellar propulsion as a promising approach for nanolocomotion. ABFs are capable of precisely 3D navigation in different liquids under weak-strength magnetic fields 1000 times lower than the fields used in clinical MRI systems. While this unique technological breakthrough has many potential applications, such as targeted drug delivery, diagnosis, and implantation or removal of tissue and objects, one of the main challenges of the microrobots, i.e. the functionality, have yet to be adequately addressed. This project directly addresses this key issue that must be solved in order to realize biomedically relevant applications. Specifically, we will develop a new process for surface functionalization of ABFs using DPPC-liposome, which are capable of loading and performing temperature-triggered releasing of their cargo payload, such as fluorescence dye for in vivo tracking and drugs for targeted delivery. In this project, we will develop feasible processes for the surface coating of ABF using DPPC liposome, to investigate the stability of the liposome-coating of the ABFs under static and dynamic conditions, and the swimming performance of DPPC-coated ABFs. After the investigation of temperature-triggered releasing of DPPC-liposome, selective single-cell transfection using these functionalized ABF (f-ABF) will be demonstrated in vitro. This study provides not only a promising approach for the functionalization of ABFs, but also fundamental basis for biomedical applications of intelligent microrobots.

无线操控的医疗微型机器人对于微创医疗有着革命性的应用前景，如靶向释药等。在各种驱动微型机器人的方法中,外磁场驱动方式非常有利于人体内应用，因为低强度磁场对于活体细胞和生物组织无害。人造细菌鞭毛(ABF)是一种通过磁场操控，模仿细菌运动的螺旋状微型机器人。迄今为止，虽然ABF的制备和磁控运动得到了大力发展，但对于执行体内医疗任务和细胞操作分析，其功能化问题必须得到解决。本项目旨在研究和发展ABF的表面功能化，首次提出以热敏脂质体(DPPC)来修饰ABF表面，使ABF不仅可以用于体外单细胞分析，也可进一步用于体内智能靶向释药。我们将研究ABF的表面修饰过程及机理，功能化器件的脂质体稳定性，游动特性和热敏性，以及实现单细胞荧光转染。基于脂质体可控释药的功能，本研究结果不仅将对ABF功能化提出一个新方案，而且将为发展智能微型机器人在体内生物医疗上的应用提供理论和实验基础。

无线操控的医疗微型机器人对于微创医疗有着革命性的应用前景，如靶向释药等。在各种驱动微型机器人的方法中,外磁场驱动方式非常有利于人体内应用，因为低强度磁场对于活体细胞和生物组织无害。人造细菌鞭毛(ABF)是一种通过磁场操控，模仿细菌运动的螺旋状微型机器人。虽然ABF 的制备和磁控运动得到了大力发展，但对于执行体内医疗任务和细胞操作分析，其功能化问题必须得到解决。..通过本国家自然科学基金资助项目我们探明了人造细菌鞭毛和DPPC脂质体的界面属性以及DPPC 热敏脂质体在修饰人造细菌鞭毛后的吸附稳定性和药物及荧光物质的装载和释放能力。利用装载荧光染料的DPPC 修饰的人造细菌鞭毛，我们研究掌握了通过控制温度释放该脂质体药物于螺旋状微型机器人表面的基本特性，如释放率。并且，我们首次利用功能化的ABF实现试管内的单细胞转染，即ABF表面的脂质体装载pDNA，首次成功进行螺旋状微型机器人ABF单细胞精度的靶向基因输送，并加深了对功能化的ABF 微型机器人靶向释药机理的理解。此外，通过力学模型，我们也进一步从理论上分析螺旋结构的力学特性，并评估磁性微型机器人对于细胞等微小物体的可操作性。..本项目的研究结果不仅将对ABF 大批量制备、功能化提出了新的解决方案，而且为发展智能微型机器人在体内生物医疗上的应用进一步提供理论和实验基础。使我国在医疗微型机器人的研发上在国际舞台上占有重要的一席之地。