Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, Republic of Korea.
ACS Appl Mater Interfaces. 2021 May 5;13(17):19633-19647. doi: 10.1021/acsami.1c01742. Epub 2021 Apr 20.
Therapeutic drug delivery microrobots capable of accurate targeting using an electromagnetic actuation (EMA) system are being developed. However, these drug delivery microrobots include a large number of magnetic nanoparticles (MNPs) for accurate EMA targeting, which causes side effects, such as problems with membrane integrity and normal cell apoptosis. Here, a biocompatible and hydrolyzable PEGDA-based drug delivery helical microrobot capable of MNP retrieval is proposed in which doxorubicin (DOX), an anticancer drug, is encapsulated and MNPs are conjugated by a disulfide bond. After being accurately delivered to the lesion of cancer cells through magnetic field manipulation, the fabricated microrobot provides rapid MNP separation and retrieval from the microrobot because of the use of dithiothreitol (DTT), a reducing agent, as an environment similar to the surrounding cancer cells and near-infrared (NIR) as an external stimulus. The characteristics of the fabricated microrobot are analyzed, and fundamental tests for active electromagnetic field manipulation, separation/retrieval of MNPs from the microrobot, and its hydrolysis are discussed. The therapeutic performance of the fabricated microrobot is verified through an test using tumor cells. Consequently, by use of an integrated system of microscope, eight-coil EMA, and NIR it is shown that the proposed microrobot can be moved to the target site by electromagnetic manipulation. The MNPs conjugated to the microrobot can be separated and retrieved, and the therapeutic effect on tumor cells by the encapsulated drug can be seen.
正在开发能够通过电磁致动（EMA）系统进行精确靶向的治疗性药物输送微机器人。然而，这些药物输送微机器人包含大量用于精确 EMA 靶向的磁性纳米颗粒（MNP），这会引起副作用，例如膜完整性和正常细胞凋亡问题。在这里，提出了一种基于生物相容性和可水解的 PEGDA 的药物输送螺旋微机器人，它能够回收 MNP，其中包裹了阿霉素（DOX），一种抗癌药物，并且通过二硫键将 MNPs 连接。通过磁场操纵精确输送到癌细胞病变部位后，由于使用二硫苏糖醇（DTT）作为类似于周围癌细胞的环境以及近红外（NIR）作为外部刺激，制造的微机器人能够快速从微机器人中分离和回收 MNP。分析了制造的微机器人的特性，并讨论了主动电磁场操纵、从微机器人中分离/回收 MNPs 以及其水解的基本测试。通过使用肿瘤细胞的 测试验证了制造的微机器人的治疗性能。因此，通过显微镜、八线圈 EMA 和近红外光的集成系统，表明所提出的微机器人可以通过电磁操纵移动到目标部位。可以分离和回收连接到微机器人上的 MNPs，并且可以看到封装药物对肿瘤细胞的治疗效果。
