微纳米马达在药物递送中的应用

受到自然界中高效生物马达的启发,研究人员提出了人工微纳米马达的概念,即人工微纳米动力装置。目前,通过结合化学与其他交叉学科的先进技术,研究人员已制备出具有不同结构、驱动方式以及控制方式的人工微纳米马达。这些微纳米马达在传感、环境治理、生物医用等方面展现出广阔的应用前景。其中,药物递送是生物医用领域的重要方向。在这一方面,利用微纳米马达可以实现药物的有效递送,给癌症等疾病的治疗带来新的可能。本文将针对用于药物递送的微纳米马达的驱动机理、基本结构、运动控制这几个方面进行综述,首先介绍了马达的运动机理,其驱动机理可分为自场驱动和外场驱动;其次,分别介绍了可用于药物递送的微纳米马达的结构,主要包括聚合物囊泡、空心管、纳米线等;为了实现精准有效的药物递送,微纳米马达的可控运动非常重要,本文将具体阐述微纳米马达的开-关控制、方向控制和速度控制。最后,分析了药物递送微纳米马达的研究现状,并对本领域的未来方向进行了展望。     

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。     

可控分子组装的自驱动胶体马达及其生物医学应用

人造胶体马达是能够将不同形式的能量转化为流体中机械运动的微纳米机器.自2 0 1 2年以来,将自下而上的可控分子组装与自上而下的方法有效结合已成为可控构筑胶体马达的重要策略之一.基于可控分子组装(如层层组装)的胶体马达具有易于实现规模化制备、能够对外界刺激作出响应、便于实现多功能化等优点.本文综述了通过将各种功能性构筑基元集成到组装结构中进而实现胶体马达的可控构筑、运动控制以及生物医学应用等方面的研究进展.主要介绍了基于不同层层组装结构的气泡驱动马达的可控构筑,基于聚电解质多层膜微胶囊及纳米管的近红外光驱动马达的构筑,生物界面化马达的制备,实现对胶体马达运动速度、方向及状态有效控制的主要方法,以及马达在药物靶向递送、光热治疗和生物毒素清除等生物医学领域中的应用.     

介孔二氧化硅基智能递送体系的构建及其在各类疾病治疗中的应用

利用先进纳米技术开发的药物递送体系能够改善药物的理化性质和治疗效果,同时削弱其毒副作用,因而纳米药物递送体系成为现代药剂学研究的热点和主流方向。其中,介孔二氧化硅作为纳米载体的基质材料具有比表面积大、形貌结构可调、表面易于修饰及生物相容性良好等优点,引发生物医学研究人员的广泛关注,为构筑新型智能药物递送体系提供了新的设计思路。本文就介孔二氧化硅基智能递送体系在设计构筑和疾病治疗应用等方面的最新研究进展进行了综述。首先,本文对介孔硅的发展历程、制备方法及结构特性进行了简要概述;其次,从药物装载和门控释放两大角度系统阐述了近些年介孔硅基智能递送体系的构建策略,重点介绍了各种刺激响应性介孔硅基递送体系的门控开关(如聚合物、无机纳米颗粒、超分子组装体及生物大分子等)及其可控释放机制;随后,详细描述了介孔硅基控释体系在各种类型疾病(包括癌症、细菌感染、糖尿病和阿尔茨海默病等)治疗中的应用进展;最后,总结和分析了介孔硅基智能纳米载体研究中存在的问题并对其未来发展作了展望。     

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。     

磁应答型药物递送载体的设计与构建

复合磁性生物材料的发展和应用已引起生物医学领域的极大关注。磁性纳米粒子因其易功能化而具有靶向药物传递、可控药物释放及磁成像特性逐渐成为药物传递和新型诊疗领域最有前途的材料之一。基于磁性纳米粒子或掺杂的铁氧化物构建的远程触发磁性载药递送系统,有望实现在运输过程中携载药物不泄露的情况下,提高药物递送效率且对病灶周围的健康细胞无毒或低毒性。为构建理想的可控靶向磁性药物递送系统,多种材料或配体可以与磁性纳米粒子复合来构建更安全有效的磁性药物递送系统。一些生物分子、聚合物及天然产物等通过与磁性纳米粒子相结合,构建出可用于药物传递且具有独特性质的磁性复合新材料。迄今为止,具有磁场应答能力的磁性药物递送载体已经在远程控制药物释放领域得到了长足发展。本文总结了近年来磁性药物递送载体作为远程控制治疗体系在设计与构建上的研究进展。重点关注了磷脂分子、聚合物、多孔微纳米材料以及天然产物等与其构建的复合材料,并对当前磁性复合特定给药载体的优点、局限及发展前景等做了简要阐述。     

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。     

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.     

天然多糖作为核酸载体的研究

基因治疗这种堪称革命性的治疗方法,开拓了治疗癌症的新思路,其最关键性问题是实现核酸药物靶向肿瘤组织并精准治疗。核酸药物直接递送存在核酸酶降解代谢、细胞膜上的负电荷排斥现象以及稳定性差等问题,所以核酸药物需要载体协助,成功的载体递送除能使核酸药物在肿瘤区域大量富集外,还要起到药物控释作用,而天然多糖除无毒、生物相容度高、易修饰的特点外,它本身就具有免疫调节、抗肿瘤、抗炎等多种生物活性。本篇总结了最具代表性的五种多糖的结构特征及在核酸药物递送方面的应用,继而归纳了多糖的常用的纳米级载体形式,为构建天然多糖递送核酸的新型载体并将其应用到免疫抗肿瘤治疗研究中奠定基础。     

铂类抗癌药物的多功能纳米递送体系

以顺铂为代表的小分子铂类抗癌药物是临床应用的一线化疗药物,但其严重的毒副作用和难以克服的耐药性限制了铂类药物的临床应用和研发。运用纳米药物递送技术可以实现药物的靶向递送和可控释放,来提高药物的生物利用度,降低药物的毒副作用以及耐药性,为癌症的治疗带来新的希望。此外,丰富多样的纳米递送体系易于实现药物与具有生物学活性试剂的共运输,从而为各种治疗策略以及诊疗策略的联用提供可能,为最终实现癌症的精准治疗展现广阔前景。本文从靶向递药、药物可控释放、联合治疗、诊疗一体化四个方面对铂类抗癌药物的多功能纳米递送体系在癌症治疗中的最新研究进展进行综述,同时通过列举最新研究成果,展示了新材料、新技术以及新颖设计思想在铂基纳米递送体系中的应用。     

Motion Control of Micro‐/Nanomotors

As we progress towards employing self‐propelled micro‐/nanomotors in envisioned applications such as cargo delivery, environmental remediation, and therapeutic treatments, precise control of the micro‐/nanomotors direction and their speed is essential. In this Review, major emerging approaches utilized for the motion control of micro‐/nanomotors have been discussed, together with the lastest publications describing these approaches. Future studies could incorporate investigations on micro‐/nanomotors motion control in a real‐world environment in which matrix complexity might disrupt successful manipulation of these small‐scale devices.     

Micro/Nanomotors for Water Purification

Self-propelled micro/nanomotors are synthetic machines that can convert different sources of energy into motion; at the same time, they are able to serve innovative environmental applications, for example, water purification. The self-propelled micro and nanomachines can rapidly zoom through the solution, carrying catalytic surface or chemical to remove or degrade pollutants in a much faster fashion than that of static systems, which depend on diffusion and fluxes. This review highlights the recent progress of micro/nanomotors in water pollutant detection and pollutant removal 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.     

Chemically Powered Micro‐ and Nanomotors

Chemically powered micro‐ and nanomotors are small devices that are self‐propelled by catalytic reactions in fluids. Taking inspiration from biomotors, scientists are aiming to find the best architecture for self‐propulsion, understand the mechanisms of motion, and develop accurate control over the motion. Remotely guided nanomotors can transport cargo to desired targets, drill into biomaterials, sense their environment, mix or pump fluids, and clean polluted water. This Review summarizes the major advances in the growing field of catalytic nanomotors, which started ten years ago.     

One Modification,Two Functions: Single Ni‐modified Light‐Driven ZnO Microrockets with Both Efficient Propulsion and Steerable Motion

Efficient propulsion and effective direction control are essential for self‐propelled micro/nanomotors. Here, a new “two‐in‐one” strategy for making attractive light‐driven micro/nanomotors is demonstrated. We make use of the metallic and magnetic properties of low‐cost Ni and incorporate just a single Ni layer into ZnO‐based microrockets, so that the resulting ZnO‐Ni microrockets can be both efficiently propelled by low energy (low light intensities and fuel concentrations) and effectively steered by a magnetic field. This successful demonstration of ZnO‐Ni microrockets is significant for the development of highly efficient synthetic micro/nanomotors, which have strong delivery ability and efficient direction control for future applications across the micro/nanoscale field.     

Motion-driven sensing and biosensing using electrochemically propelled nanomotors

Electrochemically-propelled nanomotors offer considerable promise for developing new and novel bioanalytical and biosensing strategies based on the direct isolation of target biomolecules or changes in their movement in the presence of target analytes. For example, receptor-functionalized nanomotors offer direct and rapid target isolation from raw biological samples without preparatory and washing steps. Microtube engines functionalized with ss-DNA, aptamer or antibody receptors are particularly useful for the direct isolation of nucleic acids, proteins or cancer cells, respectively. A new nanomotor-based signal transduction involving measurement of speed and distance travelled by nanomotors, offers highly sensitive, rapid, simple and low cost detection of target biomarkers, and a new dimension of analytical information based on motion. The resulting distance signals can be easily visualized by optical microscope (without any sophisticated analytical instrument) to reveal the target presence and concentration. The attractive features of the new micromachine-based target isolation and signal transduction protocols reviewed in this article offer numerous potential applications in biomedical diagnostics, environmental monitoring, and forensic analysis.     

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.     

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.     

Design and Fabrication of Tubular Micro/Nanomotors via 3D Laser Lithography

Catalytic tubular micro/nanomachines convert chemical energy from a surrounding aqueous fuel solution into mechanical energy to generate autonomous movements, propelled by the oxygen bubbles decomposed by hydrogen peroxide and expelled from the microtubular cavity. With the development of nanotechnology, micro/nanomotors have attracted more and more interest due to their numerous potential for in vivo and in vitro applications. Here, highly efficient chemical catalytic microtubular motors were fabricated via 3D laser lithography and their motion behavior under the action of driving force in fluids was demonstrated. The frequency of catalytically‐generated bubbles ejection was influenced by the geometrical shape of the micro/nanomotor and surrounding chemical fuel environment, resulting in the variation in motion speed. The micro/nanomotors generated with a rocket‐like shape displayed a more active motion compared with that of a single tubular micro/nanomotor, providing a wider range of practical micro‐/nanoscale applications in the future.     

Systematic Research and Evaluation Models of Nanomotors for Cancer Combined Therapy

Limited tumor permeability of therapeutic agents is a great challenge faced by current cancer therapy methods. Herein, a kind of near infrared light (NIR)‐driven nanomotor with autonomous movement, targeted ability, hierarchical porous structure, multi‐drugs for cancer chemo/photothermal therapy is designed, prepared and characterized. Further, we establish a method to study the interaction between nanomotors and cells, along with their tumor permeability mechanism, including 2D cellular models, 3D multicellular tumor spheroids and in vivo models. In vivo tumor elimination results verify that the movement behaviour of the nanomotors can greatly facilitate them to eliminate tumor through multiple therapeutic methods. This work tries to establish systematic research and evaluation models, providing strategies to understand the relationship between motion behaviour and tumor permeation efficiency of nanomotors in depth.