聚合物短纤维基微纳马达的运动特性及生物医学功能

We have investigated previously electrospun fibrous mats and their biomedical application. This proposal is aimed to explore self-propelled short fibers, providing solutions for efficient drug delivery and effective separation and detection of biological substances. Three types of micro- and nanomotors (MNMs) are constructed with motion and navigation features, including enzyme-motivated Janus short fibers, bacteria-propelled hollow short fibers and magnetic field-driven helical short fibers. This study focuses on the clarification of motion profiles of short fibers-derived MNMs, realizing the motion control via short fiber characteristics, power sources and motion media. The MNMs as drug delivery carriers take advantages of the multiple shapes (plates, rods and wires) of Janus short fibers and bacterial chemotaxis to hypoxic regions of tumor tissues. To enhance the targeting delivery of chemotherapeutic agents, the impact mechanism of motion profiles is studied on the penetration into tumor tissues from blood circulation of MNMs, followed by the distribution within tumor microenvironment and the function on tumor cells. MNMs derived from Janus and helical short fibers are grafted with capture and visual ligands for separation and biosensing of molecules and cells. The recognizing, tracing and detection efficiencies are promoted by the motion of MNMs as well as the multiple point adhesion between short fibers and cells and the ratiometric response of fluorescent intensities and color transitions. Therefore, the motion profiles of MNMs are essential to enhance the biomedical function of short fibers, and the elucidation of their interaction mechanism lays a theoretic and technological foundation for the development of tumor treatment and biosensing strategies.

在前期电纺纤维生物医学功能研究的基础上，本申请拟研究自驱运动的聚合物短纤维，为高效的药物输送和分离检测提供解决方案。创建三类兼具运动和导航能力的聚合物短纤维基微纳马达，即双面（Janus）短纤维/酶、中空短纤维/细菌、螺旋短纤维/磁场等。围绕一个中心，即认知短纤维基微纳马达的运动特性，掌握运动行为的调控手段及对生物医学功能的影响机制。利用Janus短纤维的性状多样性（饼、柱和线）、细菌对肿瘤组织的趋向性等，研究载药马达的运动行为对渗透进入肿瘤组织、在组织中扩散、以及作用于肿瘤细胞等过程的影响机制，提升药物的靶向输送能力。以Janus和螺旋短纤维基微纳马达为对象，通过接枝捕获和显色配体，利用短纤维与细胞的多点位结合、荧光强度比率分析等，增强微纳马达对生物分子和细胞的捕获分离、示踪检测效能。总之，通过揭示微纳马达的运动特性提升短纤维生物医学功能的实现机制，发展肿瘤治疗和生物传感的策略和手段。

在药物递送和生物分离检测等领域中，迫切需要载体粒子具有在微纳米乃至宏观尺寸上运动的能力。项目研究围绕一个中心（短纤维基微纳马达的运动特性调控及对生物医学功能的影响机制），构建了三类棒状微纳马达（Janus短纤维微纳马达、细菌马达、中空结构微马达），探究了两种功能的实现机制（促进药物送达效率、增强分离检测效果）。研究工作主要包括四个方面，一是Janus结构短纤维微马达的生物分离检测功能。采用“肩-并-肩”电纺法制备了Janus短纤维，一侧固定化酶驱动马达运动，另一侧修饰能识别被检物的功能基团；微纳马达的持续运动实现了目标物质的快速分离富集和灵敏检测。二是Janus结构短纤维微纳马达的药物载体功能。采用物理气相沉积制备Janus结构二氧化硅纳米粒子，利用电纺法制备Janus短纤维，基于介孔二氧化硅在羟基磷灰石短棒一侧的种子生长制备Janus纳米短棒，再在一侧固定化酶驱动马达运动；微纳马达的运动性促进了血管穿透、组织扩散和肿瘤细胞吞噬等系列过程，同时拓展到溶栓和抗菌体系中。三是细菌微马达作为药物载体。以药物携载量和释放机制为研究主线，通过在细菌表面接枝药物或载药胶束的前体分子，或在一定条件下转换成细菌影的内部空腔载药等方式提升载药量；为综合利用细菌的运动性、靶向性和细菌影的高载药能力，提出了活菌装载药物、运动至肿瘤组织后原位变成细菌影的思路；载药细菌的运动特性促进了药物在肿瘤组织中的富集和抗肿瘤效果。四是中空结构微马达的药物载体功能。以聚碳酸酯微孔膜、电纺短纤维和细菌为模板，经聚合物的逐层沉积或多巴胺的原位聚合等制备微管，再通过组装细菌或装载酶等作为动力源，构建了类似火箭的中空结构微马达，提升了肿瘤治疗和溶栓效果。项目研究已发表SCI收录论文35篇，发表论文已被SCI他引400余次。总之，项目研究揭示了微纳马达运动特性提升生物医学功能的实现机制，发展了肿瘤治疗和生物传感的策略和手段。