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Light-Triggered Drug Release from 3D-Printed Magnetic Chitosan Microswimmers
ACS Nano ( IF 17.1 ) Pub Date : 2018-09-11 00:00:00 , DOI: 10.1021/acsnano.8b05997
Ugur Bozuyuk 1 , Oncay Yasa 2 , I. Ceren Yasa 2 , Hakan Ceylan 2 , Seda Kizilel 1 , Metin Sitti 2
Affiliation  

Advances in design and fabrication of functional micro/nanomaterials have sparked growing interest in creating new mobile microswimmers for various healthcare applications, including local drug and other cargo (e.g., gene, stem cell, and imaging agent) delivery. Such microswimmer-based cargo delivery is typically passive by diffusion of the cargo material from the swimmer body; however, controlled active release of the cargo material is essential for on-demand, precise, and effective delivery. Here, we propose a magnetically powered, double-helical microswimmer of 6 μm diameter and 20 μm length that can on-demand actively release a chemotherapeutic drug, doxorubicin, using an external light stimulus. We fabricate the microswimmers by two-photon-based 3D printing of a natural polymer derivative of chitosan in the form of a magnetic polymer nanocomposite. Amino groups presented on the microswimmers are modified with doxorubicin by means of a photocleavable linker. Chitosan imparts the microswimmers with biocompatibility and biodegradability for use in a biological setting. Controlled steerability of the microswimmers is shown under a 10 mT rotating magnetic field. With light induction at 365 nm wavelength and 3.4 × 10–1 W/cm2 intensity, 60% of doxorubicin is released from the microswimmers within 5 min. Drug release is ceased by controlled patterns of light induction, so as to adjust the desired release doses in the temporal domain. Under physiologically relevant conditions, substantial degradation of the microswimmers is shown in 204 h to nontoxic degradation products. This study presents the combination of light-triggered drug delivery with magnetically powered microswimmer mobility. This approach could be extended to similar systems where multiple control schemes are needed for on-demand medical tasks with high precision and efficiency.

中文翻译:

3D打印的磁性壳聚糖微泳剂的光触发药物释放

在设计和功能的微加工进展/纳米材料已经引发了创造各种医疗应用,包括局部药物和其他货物(新的移动microswimmers日益增长的兴趣ê,基因,干细胞和显像剂)递送。这种基于微游泳者的货物输送通常是通过从游泳者身体扩散货物材料而被动地进行的。但是,控制货物的主动释放对于按需,精确和有效地交付至关重要。在这里,我们提出了一种直径为6μm,长度为20μm的磁动力双螺旋微掠器,可以使用外部光刺激按需主动释放化疗药物阿霉素。我们通过磁性聚合物纳米复合材料形式的壳聚糖的天然聚合物衍生物的基于两个光子的3D打印来制造微泳者。通过光可裂解的连接子,用阿霉素修饰存在于微泳剂上的氨基。壳聚糖赋予微游泳者以生物适应性和生物降解性。在10 mT旋转磁场下显示了微游泳器的可控转向性。在365 nm波长和3.4×10的光感应下强度为–1 W / cm 2,在5分钟内从微游泳器中释放出60%的阿霉素。药物释放通过光诱导的受控模式停止,从而在时域中调节所需的释放剂量。在生理上相关的条件下,微游泳器在204小时内会大量降解为无毒降解产物。这项研究提出了光触发给药与磁动力微游泳机移动性的结合。这种方法可以扩展到类似的系统,在这些系统中,需要多个控制方案来实现按需医疗任务的高精度和高效率。
更新日期:2018-09-11
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