面向疾病应用的微纳米马达

微纳米马达是能将环境中的化学反应或外场(光、声、磁场、电场等)提供的能量转化为推进力,从而产生自主运动的微纳米级人造机器。由于具有集群效应、比表面积大、运动可控等多种特征,微纳米马达在环境修复、药物递送、微纳手术、抗感染、重金属清除等诸多领域受到关注。在一定条件下,微纳米马达能主动运动并聚集到病灶,将治疗或诊断药物递送到靶部位,有望在人体复杂环境中进行精细化的工作。因此,微纳米马达在疾病预防、诊断、治疗以及预后中具有巨大的发展空间。在此,本综述首先对微纳米马达进行简要介绍,包括其结构设计、驱动方式。其次,详细介绍微纳米马达在不同类型的疾病中的研究进展。最后,提出目前该技术面临的挑战与未来发展方向。     

微/纳米马达在生物传感中的应用

微/纳米马达是近年来发展的一种可自主运动的新型微/纳米材料,它制备简单、形态多样、可批量化生产,已逐渐应用于生物样品分析及药物运输等领域。由于生物样品成分复杂,传统检测常常需要多步清洗和分离,操作繁琐、耗时较长。微/纳米马达具有自主运动的特性,通过表面生物功能化,可制备成动态的微型生物传感器,实现多种生物分子如核酸、蛋白质、糖蛋白等的实时、快速和灵敏检测。本文总结了近几年微/纳米马达的发展及其在生物传感中的应用,并展望了其在生物分析中的应用前景。     

生物酶驱动的微纳米马达在生物医学领域的应用

生物酶驱动微纳米马达是指利用天然酶催化分解过氧化氢、葡萄糖、尿素和甘油酯等燃料来提供动力的一种新型微纳米机器。生物酶驱动的微纳米马达具有良好的生物相容性,能够在原位利用生物燃料实现自主靶向运动,无需外加原料,这使得生物酶驱动的微纳米马达在生物医学领域展现出巨大的发展潜力与前景。目前,生物酶驱动的微纳米马达在生物医学领域的应用得到众多科学家的关注,但是时至今日,还没有一篇及时、全面、着重地讨论生物酶驱动微纳米马达在生物医学领域应用的综述文章。基于本课题组的研究经验以及目前该领域的发展情况,本文着重讨论不同种类生物酶驱动微纳米马达在疾病诊疗等生物医学领域应用的最新进展,包括生物标志物的检测与诊断、成像显像剂、癌症和其他疾病的治疗等。最后,本文对该领域的发展与未来研究方向提出展望,为实现以“面向世界科技前沿、面向人民生命健康”为目标的“人类卫生健康共同体”提供新的思路和方向。     

纳米金属有机框架材料在药物递送领域的应用

金属有机框架材料(Metal-Organic Frameworks, MOFs)是一类由金属离子及有机配体自组装而成的多孔材料,具有孔隙率高、比表面积大和结构多样化等独特优点,广泛应用于气体储存、物质分离和催化等领域。纳米尺寸金属有机框架材料(Nanoscale Metal-Organic Frameworks, NMOFs)既保持了传统MOFs的规整性,也具有纳米颗粒的特殊性质,在生物医药领域中是绝佳的药物载体。相比于传统纳米药物载体,NMOFs与药物的结合方式丰富,展现了多种药物装载模式,可以满足不同药物的制备需求,也可引入不同功能分子优化性能。最近,有越来越多的研究报道了多功能化NMOFs应用于药物递送领域,并实现刺激响应性的可控释放。本文将着重对NMOFs材料作为药物载体负载抗癌药物、光敏剂和核酸的应用进展进行综述。     

胶体粒子的机械性能调控及其在药物递送中的应用

胶体粒子是肿瘤治疗中最常用的载体, 尽管在过去的研究中不同的胶体粒子已经被广泛报道, 但如何进一步提高胶体粒子的药物递送效率仍然存在着一些挑战. 大量的研究表明胶体粒子的尺寸、形状、结构和表面化学等物理化学性质在药物递送过程中具有重要的作用, 但胶体粒子的机械性能对药物递送过程的影响研究和综述相对较少. 本综述从不同机械性能胶体粒子的制备与表征出发, 概述了胶体粒子的机械性能对血液循环、肿瘤富集、渗透以及细胞内化过程的影响, 并对该领域存在的问题以及发展的趋势进行了展望. 该综述有助于帮助科学工作者更好地理解胶体粒子的机械性能对药物递送的影响规律, 从而优化胶体粒子的设计并提高纳米药物的递送效率和生物利用率.     

药物递送中的高分子原理

药物递送正在逐渐成熟为一门工程科学,主要根据药理学的要求,利用材料科学的基本原理来进行递送体系设计和研究.高分子是药用材料的主要类别,本文以药物一高分子固体分散体和高分子药物为例,讨论了高分子科学中的基本原理,尤其是结构与性能关系,是如何在药物递送研究和设计中得以体现的.另一方面,药物递送领域的发展也对高分子科学提出了...     

肝素在抗肿瘤药物递送系统中的应用

肝素是一种高度硫酸化的糖胺聚糖,目前主要作为抗凝剂应用于临床。肝素具有一定的抗肿瘤转移的作用,而基于肝素此项功能的抗肿瘤药物递送系统亦被广泛研究。在这类药物传递系统中,肝素一方面可增强抗肿瘤药物的抑瘤效果,同时亦可发挥自身的抗肿瘤转移功能,使药物及载体协同作用。基于肝素的抗肿瘤转移作用机理及肝素在药物递送系统中的应用,围绕相关的设计思路与方法展开综述,以期为相关领域的研究提供参考。     

仿生螺旋结构微马达研究进展

微型马达是对传统马达系统的功能拓展和有益补充,在污水处理、环境监测修复、靶向手术和药物输送等方面拥有潜在应用前景。在流体环境中,高效率驱动性能是微型马达面临的重要挑战。依据理论和研究实践,人们普遍选择仿生螺旋结构作为马达的微驱动策略,并取得诸多新进展。本文从螺旋结构驱动的理论研究、螺旋微结构制备方法、螺旋马达的驱动机制和应用基础研究等几个方面系统性综述了该领域近年的进展情况。最后提出了当前研究中亟待解决的科学问题并展望了未来重点研究方向。     

苯硼酸功能化聚合物纳米载体用于蛋白质药物胞内递送

蛋白质药物在疾病治疗方面具有广泛应用,但它们的低细胞膜穿透性往往导致生物利用度较低.近年来,人们开发了一系列纳米载体用于提高蛋白质药物的胞内递送效率,其中基于苯硼酸及其衍生物的聚合物纳米载体显示出良好的应用前景.本文综述了苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的最新研究进展.首先,简要介绍了苯硼酸的化学性质及其二醇、pH和活性氧(ROS)响应性.其次,从苯硼酸与蛋白质药物的结合方式不同出发,重点综述了通过动态共价作用和N→B配位等非共价作用构筑的苯硼酸功能化聚合物纳米载体在蛋白质药物胞内递送方面的典型研究实例,并对这些载体的组成、构筑方式和响应性释放机制进行了分析、总结.最后,介绍了利用苯硼酸增强细胞摄取和促进药物透过血脑屏障方面的研究进展.希望能为设计制备基于苯硼酸的新型蛋白质药物胞内递送体系提供借鉴.     

兼具抗癌和药物递送作用的硒掺杂羟基磷灰石微球

利用碳酸钙作为处理模板,通过共沉淀联合水热法,制备了硒元素掺杂羟基磷灰石微球(HASe),期望硒掺杂能提高HA对溶菌酶的加载,并增强HASe微球的杀菌活性。所合成的HASe微球经SEM、TEM、DLS、XRD、FTIR和TGA测试对其理化性能进行了表征。并且利用姜黄素作为模式药物,评估了它们的药物加载及控释效能。结果发现,所合成的HASe产物为直径约1.0μm的球体,球壁粘附有许多羟基磷灰石纳米棒(长约150 nm﹑宽约20 nm)。该HASe微球对姜黄素具有高的药物加载和缓慢稳定的控释效应。其药物加载量为(88.72±0.01)mg·g~(-1),在0~159 h内仅有不到1.5 mg的姜黄素被释放,且无爆释现象。此外,还通过血液分析和细胞实验评估了HASe微球的毒性行为。与无硒HA微球相比,HASe微球的血液毒性低,对细胞损伤少,然而对骨肉瘤细胞生长却具有强的抑制作用。     

基于微/纳马达的智能癌症诊断、递送及治疗

癌症严重威胁着人类的生命健康,早期的诊断和治疗对于提高癌症治愈率、挽救人们的生命有着至关重要的作用。随着纳米科技的发展,具有自主运动性能的微/纳马达为癌症的诊断与治疗带来了新的发展契机。微/纳马达能够有效地将多种能量(光、声、磁、电、热等)转化为自身运动的动能,有望在微米或纳米空间内执行各种复杂而精确的任务,这在智能化癌症诊疗领域具有得天独厚的优势。目前,已成功制备出不同形状的微/纳马达,比如线状马达、微管马达、Janus双面神结构马达等,促进了一系列新型诊断方法、胞内递送系统及光治疗策略等的发展。本文主要总结了微/纳马达在智能化癌症诊疗领域的研究进展,首先从化学场驱动与物理场驱动这两个角度总结了微/纳马达在检测和靶向递送方面的最新研究进展,并进一步总结了微/纳马达在癌症光治疗领域的应用进展,最后探讨了目前存在的问题及未来的发展方向。     

Turn‐Number‐Dependent Motion Behavior of Catalytic Helical Carbon Micro/Nanomotors

Helical micro/nanomotors (MNMs) can be propelled by external fields to swim through highly viscous fluids like complex biological environments, which promises miniaturized robotic tools to perform assigned tasks at small scales. However, the catalytic propulsion method, most widely adopted to drive MNMs, is seldom studied to actuate helical MNMs. Herein, we report catalytic helical carbon MNMs (CHCM) by sputtering Pt onto helical carbon nano‐coils (HCNC) that are in bulk prepared by a thermal chemical vapor deposition method. The Pt‐triggered H₂O₂ decomposition can drive the MNMs by an electrokinetic mechanism. The MNMs demonstrate versatile motion behaviors including both directional propulsion and rotation depending on the turn number of the carbon helix. Besides, due to the ease of surface functionalization on carbon and other properties such as biocompatibility and photothermal effect, the helical carbon MNMs promise multifunctional applications for biomedical or environmental applications.     

Redox-Sensitive Stomatocyte Nanomotors: Destruction and Drug Release in the Presence of Glutathione

The development of artificial nanomotor systems that are stimuli-responsive is still posing many challenges. Herein, we demonstrate the self-assembly of a redox-responsive stomatocyte nanomotor system, which can be used for triggered drug release under biological reducing conditions. The redox sensitivity was introduced by incorporating a disulfide bridge between the hydrophilic poly(ethylene glycol) block and the hydrophobic polystyrene block. When incubated with the endogenous reducing agent glutathione at a concentration comparable to that within cells, the external PEG shells of these stimuli-responsive nanomotors are cleaved. The specific bowl-shaped stomatocytes aggregate after the treatment with glutathione, leading to the loss of motion and triggered drug release. These novel redox-responsive nanomotors can not only be used for remote transport but also for drug delivery, which is promising for future biomedical applications.     

Biocatalytic Micro- and Nanomotors

Enzyme-powered micro- and nanomotors are tiny devices inspired by nature that utilize enzyme-triggered chemical conversion to release energy stored in the chemical bonds of a substrate (fuel) to actuate it into active motion. Compared with conventional chemical micro-/nanomotors, these devices are particularly attractive because they self-propel by utilizing biocompatible fuels, such as glucose, urea, glycerides, and peptides. They have been designed with functional material constituents to efficiently perform tasks related to active targeting, drug delivery and release, biosensing, water remediation, and environmental monitoring. Because only a small number of enzymes have been exploited as bioengines to date, a new generation of multifunctional, enzyme-powered nanorobots will emerge in the near future to selectively search for and utilize water contaminants or disease-related metabolites as fuels. This Minireview highlights recent progress in enzyme-powered micro- and nanomachines.     

Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound‐Propelled Nanomotors

Direct and rapid intracellular delivery of a functional Cas9/sgRNA complex using ultrasound‐powered nanomotors is reported. The Cas9/sgRNA complex is loaded onto the nanomotor surface through a reversible disulfide linkage. A 5 min ultrasound treatment enables the Cas9/sgRNA‐loaded nanomotors to directly penetrate through the plasma membrane of GFP‐expressing B16F10 cells. The Cas9/sgRNA is released inside the cells to achieve highly effective GFP gene knockout. The acoustic Cas9/sgRNA‐loaded nanomotors display more than 80 % GFP knockout within 2 h of cell incubation compared to 30 % knockout using static nanowires. More impressively, the nanomotors enable highly efficient knockout with just 0.6 nm of the Cas9/sgRNA complex. This nanomotor‐based intracellular delivery method thus offers an attractive route to overcome physiological barriers for intracellular delivery of functional proteins and RNAs, thus indicating considerable promise for highly efficient therapeutic applications.     

Fuel‐Free Micro‐/Nanomotors as Intelligent Therapeutic Agents

There are many efficient biological motors in Nature that perform complex functions by converting chemical energy into mechanical motion. Inspired by this, the development of their synthetic counterparts has aroused tremendous research interest in the past decade. Among these man‐made motor systems, the fuel‐free (or light, magnet, ultrasound, or electric field driven) motors are advantageous in terms of controllability, lifespan, and biocompatibility concerning bioapplications, when compared with their chemically powered counterparts. Therefore, this review will highlight the latest biomedical applications in the versatile field of externally propelled micro‐/nanomotors, as well as elucidating their driving mechanisms. A perspective into the future of the micro‐/nanomotors field and a discussion of the challenges we need to face along the road towards practical clinical translation of external‐field‐propelled micro‐/nanomotors will be provided.     

The Application of Micro‐ and Nanomotors in Classified Drug Delivery

Micro and nanomotors (MNMs) are micro/nanoscale devices that are able to convert chemical or external energy into mechanical motion. Based on a multitude of propulsion mechanisms, synthetic MNMs have been developed over the past decades for diverse biomedical applications, particularly drug delivery. Herein, we set out the classification of drugs delivered by MNMs, such as small molecules, nucleic acid, peptides, antibodies, and other proteins, and discuss their current limitations and possibilities in in vivo applications. Challenges and future perspectives are also discussed. With the increasing research enthusiasm in this field and the strengthening of multidisciplinary cooperation, intelligent MNMs will appear in the near future, which will have a profound impact on all related fields.     

Self‐Guided Supramolecular Cargo‐Loaded Nanomotors with Chemotactic Behavior towards Cells

Delivery vehicles that are able to actively seek and precisely locate targeted tissues using concentration gradients of signaling molecules have hardly been explored. The directed movement toward specific cell types of cargo‐loaded polymeric nanomotors along a hydrogen peroxide concentration gradient (chemotaxis) is reported. Through self‐assembly, bowl‐shaped poly(ethylene glycol)‐b‐polystyrene nanomotors, or stomatocytes, were formed with platinum nanoparticles entrapped in the cavity while a model drug was encapsulated in the inner compartment. Directional movement of the stomatocytes in the presence of a fuel gradient (chemotaxis) was first demonstrated in both static and dynamic systems using glass channels and a microfluidic flow. The highly efficient response of these motors was subsequently shown by their directional and autonomous movement towards hydrogen peroxide secreting neutrophil cells.