Light-Triggered Drug Release from 3D-Printed Magnetic Chitosan Microswimmers
Light-Triggered Drug Release from 3D-Printed Magnetic Chitosan Microswimmers
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DOI：
10.1021/acsnano.8b05997
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发表时间：
2018-09-01
期刊：
影响因子：
17.1
通讯作者：
Sitti, Metin
中科院分区：
文献类型：
--
作者：
Bozuyuk, Ugur;Yasa, Oncay;Sitti, Metin
功能性微米/纳米材料的设计和制造的进步已经引发了人们对创建用于各种医疗保健应用的新的移动的微泳者的日益增长的兴趣，包括本地药物和其他货物（例如，基因、干细胞和显像剂）递送。这种基于微游泳器的货物递送通常通过货物材料从游泳器身体的扩散而被动;然而，货物材料的受控主动释放对于按需、精确和有效的递送是必不可少的。在这里，我们提出了一种磁动力，双螺旋microswimmer的6 pm直径和20 pm的长度，可以按需主动释放化疗药物，阿霉素，使用外部光刺激。我们通过基于双光子的3D打印以磁性聚合物纳米复合材料形式的天然聚合物衍生物壳聚糖来制造微游泳者。在微泳者上呈现的氨基通过可光裂解的连接体用阿霉素修饰。壳聚糖赋予微泳者生物相容性和生物降解性，用于生物环境。在10 mT的旋转磁场下显示了微泳者的受控可操纵性。在365 nm波长和3.4 × 10（-1）W/cm（2）强度的光诱导下，60%的阿霉素在5 min内从微泳体释放。通过控制光诱导模式来停止药物释放，以便在时间域中调整所需的释放剂量。在生理学相关条件下，在204 h内，微泳者大量降解为无毒降解产物。本研究提出了光触发药物输送与磁力驱动的微型游泳器的流动性相结合。这种方法可以扩展到类似的系统中，其中需要多个控制方案以实现高精度和高效率的按需医疗任务。
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 pm diameter and 20 pm 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 X 10(-1) W/cm(2) 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.