具有温度响应性的多模运动微米机器人可实现药物的精准递送和可控范围的药物释放

doi:10.12122/j.issn.1673-4254.2025.08.20

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (8): 1758-1767.doi: 10.12122/j.issn.1673-4254.2025.08.20

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具有温度响应性的多模运动微米机器人可实现药物的精准递送和可控范围的药物释放

赵旭辉¹^,²(), 刘梦然¹(), 陈曦²^,³, 黄静², 刘源², 徐海峰²

^1.湖北工业大学现代制造质量工程湖北省重点实验室，湖北武汉 430068
^2.中国科学院深圳先进技术研究院生物医学与健康工程研究所，广东深圳 518055
^3.南京邮电大学电子与光学工程学院、柔性电子（未来技术）学院，江苏南京 210023

收稿日期:2025-03-11 出版日期:2025-08-20 发布日期:2025-09-05
通讯作者: 刘梦然 E-mail:xh.zhao@siat.ac.cn;liumengran1991@163.com
作者简介:赵旭辉，在读硕士研究生，E-mail: xh.zhao@siat.ac.cn
基金资助:
国家自然科学基金(52303167);国家自然科学基金(52203152);湖北省自然科学基金(2022CFB473);广东省普通高校重点领域专项项目(2022ZDZX3047)

Synthesis of a temperature-responsive multimodal motion microrobot capable of precise navigation for targeted controllable drug release

Xuhui ZHAO¹^,²(), Mengran LIU¹(), Xi CHEN²^,³, Jing HUANG², Yuan LIU², Haifeng XU²

^1.Hubei Provincial Key Laboratory of Modern Manufacture Quality Engineering, Hubei University of Technology, Wuhan 430068, China
^2.Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
^3.College of Electronic and Optical Engineering & College of Flexible Electronics (Future Technology), Nanjing University of Posts and Telecommunications, Nanjing 210023, China

Received:2025-03-11 Online:2025-08-20 Published:2025-09-05
Contact: Mengran LIU E-mail:xh.zhao@siat.ac.cn;liumengran1991@163.com
Supported by:
National Natural Science Foundation of China(52303167)

摘要/Abstract

摘要：

目的利用温度场和磁场辅助的微流控液滴技术，合成了一种具有温度响应特性的多模运动微米机器人（MMMR），实现药物靶向递送和药物释放范围控制。方法通过将明胶与磁性微米颗粒混合后利用微流控液滴技术合成MMMR，在合成装置的设计中加入了温度场和磁场进行辅助，实现了机器人的磁各向异性结构。通过旋转均匀磁场控制MMMR沿预设路径进行大范围运动，并利用不同频率的平面旋转梯度磁场驱动MMMR进行局部圆周运动。MMMR装载模拟药物，通过加热进行药物释放。结果在垂直于平面旋转磁场的驱动下，MMMR可以实现直线运动，完成规定路径的运动。且在平面梯度旋转磁场作用下，MMMR利用旋转产生的离心力，可以实现运动半径可调的圆周运动。装载模拟药物的MMMR在磁场引导下成功到达目标位置，通过激光加热（39 ℃）融化明胶基质，精准释放药物，药物释放后，自组装的磁颗粒作为一个整体被移除。结论 MMMR具备多模态运动能力，可实现规定路径精准导航，并能够在局部动态调控药物释放范围，具有广泛的生物医学应用潜力。

关键词: 药物递送, 微米机器人, 磁各向异性, 多模运动, 微流控合成

Abstract:

Objective To synthesize a temperature-responsive multimodal motion microrobot (MMMR) using temperature and magnetic field-assisted microfluidic droplet technology to achieve targeted drug delivery and controlled drug release. Methods Microfluidic droplet technology was utilized to synthesize the MMMR by mixing gelatin with magnetic microparticles. The microrobot possessed a magnetic anisotropy structure to allow its navigation and targeted drug release by controlling the temperature field and magnetic field. In the experiment, the MMMR was controlled to move in a wide range along a preset path by rotating a uniform magnetic field, and the local circular motion was driven by a planar rotating gradient magnetic field of different frequencies. The MMMR was loaded with simulated drugs, which were released in response to laser heating. Results Driven by a rotating magnetic field, the MMMR achieved linear motion following a predefined path. The planar gradient rotating magnetic field controlled circular motion of the MMMR with an adjustable radius, utilizing the centrifugal force generated by rotation. The drug-loaded MMMR successfully reached the target location under magnetic guidance, where the gelatin matrix was melted using laser heating for accurate drug release, after which the remaining magnetic particles were removed using magnetic field. Conclusion The MMMR possesses multimodal motion capabilities to enable precise navigation along a predefined path and dynamic regulation of drug release within the target area, thus having great potential for a wide range of biomedical applications.

Key words: drug delivery, microrobot, magnetic anisotropy, multimodal motion, microfluidic synthesis

赵旭辉, 刘梦然, 陈曦, 黄静, 刘源, 徐海峰. 具有温度响应性的多模运动微米机器人可实现药物的精准递送和可控范围的药物释放[J]. 南方医科大学学报, 2025, 45(8): 1758-1767.

Xuhui ZHAO, Mengran LIU, Xi CHEN, Jing HUANG, Yuan LIU, Haifeng XU. Synthesis of a temperature-responsive multimodal motion microrobot capable of precise navigation for targeted controllable drug release[J]. Journal of Southern Medical University, 2025, 45(8): 1758-1767.

图/表 6

图1 MMMR的合成原理和药物递送原理

Fig.1 Principle of temperature-responsive multimodal motion microrobot (MMMR) synthesis and drug release. A: Principles of MMMR synthesis. B: Design and appearance of the synthesis device. C: Drug delivery principle of the MMMR capable of precise navigation and controlled drug release.

图2 MMMR的多模运动控制

Fig.2 Multimodal motion control of the MMMR. A: Magnetic control platform and control interface for linear motion control. B: Schematic diagram of linear motion of the MMMR. C: Schematic illustration of the rotating gradient magnetic field and a photograph of the device. D: Schematic diagram of circular motion of MMMR.

图3 MMMR的合成

Fig.3 Synthesis of the MMMR. A: Synthesis device of MMMR. B: Randomly dispersed particles in magnetic hydrogel beads. C: Assembled particles in magnetic hydrogel beads (Scale bar=150 μm). D: Size control principle of the hydrogel beads. E: Magnetic hydrogel beads with a diameter of 70 μm. F: Magnetic hydrogel beads with a diameter of 500 μm. G: Relationship between oil pressure and the diameter of beads. H: Relationship between magnetic hydrogel pressure and the generation frequency of beads.

图4 MMMR的局部圆周运动和药物靶向递送实验

Fig.4 Local circular motion and targeted drug delivery experiments with MMMR. A: Local circular motion principle. B: Movement of the MMMR under a rotating gradient magnetic field (Scale bar=10 mm). C: Relationship between speed of rotation and the radius of orbit. D: Relationship between magnetic field frequency and the linear motion speed of the MMMR. E: Test of the MMMR for targeted drug delivery (Scale bar=5 mm). F: Test of the MMMR for drug release and magnetic particle removal.

图5 MMMR的合成质量和生物相容性

Fig.5 Synthesis quality and biocompatibility of the MMMR. A: Fluorescence images of the MMMR co-cultured with cells for 6 h. B: Fluorescence images of the MMMR co-cultured with cells for 12 h. C: Scanning electron microscopy of the MMMR. D: Blood compatibility test of the MMMR. E: MMMR images under microscope (Scale bar=1 mm). F: Coefficient of variation (CV) analysis of the MMMR. G: Hysteresis loop test of the 3 MMMRs.

图6 MMMR在离体器官中进行药物递送

Fig.6 Experiments of the MMMR for drug delivery in isolated organs. A: Test of the MMMR for targeted drug delivery and laser heating release on the surface of the small intestine (Scale bar=5 mm). B: X-ray image of the MMMR (Scale bar=5 mm).

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具有温度响应性的多模运动微米机器人可实现药物的精准递送和可控范围的药物释放

Synthesis of a temperature-responsive multimodal motion microrobot capable of precise navigation for targeted controllable drug release

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