Li Yanfang, Dong Dingran, Qu Yun, Li Junyang, Chen Shuxun, Zhao Han, Zhang Qi, Jiao Yang, Fan Lei, Sun Dong
Department of Biomedical Engineering, City University of Hong Kong, Hong Kong SAR, 999077, China.
Center for Robotics and Automation, Shenzhen Research Institute of City University of Hong Kong, Shenzhen, 518000, China.
Small. 2023 Nov;19(44):e2301889. doi: 10.1002/smll.202301889. Epub 2023 Jul 9.
Multidrug combination therapy provides an effective strategy for malignant tumor treatment. This paper presents the development of a biodegradable microrobot for on-demand multidrug delivery. By combining magnetic targeting transportation with tumor therapy, it is hypothesized that loading multiple drugs on different regions of a single magnetic microrobot can enhance a synergistic effect for cancer treatment. The synergistic effect of using two drugs together is greater than that of using each drug separately. Here, a 3D-printed microrobot inspired by the fish structure with three hydrogel components: skeleton, head, and body structures is demonstrated. Made of iron oxide (Fe O ) nanoparticles embedded in poly(ethylene glycol) diacrylate (PEGDA), the skeleton can respond to magnetic fields for microrobot actuation and drug-targeted delivery. The drug storage structures, head, and body, made by biodegradable gelatin methacryloyl (GelMA) exhibit enzyme-responsive cargo release. The multidrug delivery microrobots carrying acetylsalicylic acid (ASA) and doxorubicin (DOX) in drug storage structures, respectively, exhibit the excellent synergistic effects of ASA and DOX by accelerating HeLa cell apoptosis and inhibiting HeLa cell metastasis. In vivo studies indicate that the microrobots improve the efficiency of tumor inhibition and induce a response to anti-angiogenesis. The versatile multidrug delivery microrobot conceptualized here provides a way for developing effective combination therapy for cancer.
多药联合疗法为恶性肿瘤治疗提供了一种有效策略。本文介绍了一种用于按需多药递送的可生物降解微型机器人的研发情况。通过将磁靶向运输与肿瘤治疗相结合，人们推测在单个磁性微型机器人的不同区域负载多种药物可以增强癌症治疗的协同效应。两种药物联合使用的协同效应大于单独使用每种药物的效应。在此，展示了一种受鱼类结构启发的3D打印微型机器人，它由三种水凝胶组件组成：骨架、头部和身体结构。骨架由嵌入聚乙二醇二丙烯酸酯（PEGDA）中的氧化铁（FeO）纳米颗粒制成，能够响应磁场以驱动微型机器人并实现药物靶向递送。由可生物降解的甲基丙烯酰化明胶（GelMA）制成的药物储存结构、头部和身体表现出酶响应性药物释放。分别在药物储存结构中携带阿司匹林（ASA）和阿霉素（DOX）的多药递送微型机器人通过加速HeLa细胞凋亡和抑制HeLa细胞转移，展现出ASA和DOX的优异协同效应。体内研究表明，微型机器人提高了肿瘤抑制效率并诱导了抗血管生成反应。本文所构思的多功能多药递送微型机器人为开发有效的癌症联合治疗方法提供了一条途径。
