magnetic navigation

  • 文章类型: Journal Article
    由于肿瘤内光热剂的积累不足以及治疗期间癌症免疫循环的逆转,光免疫疗法面临挑战。在这项研究中,一种抗PD-L1固定化磁性金纳米小屋,AuNH-2-Ab,光响应,热敏,和免疫调节特性,以有效抑制原发性肿瘤的生长,提高免疫原性细胞死亡(ICD)水平,逆转肿瘤免疫微环境(TIME),并因此抑制转移发展。AuNH-2-Ab在全身给药后实现高肿瘤积累(9.54%注射剂量),允许在肿瘤中调节超过50°C的热疗剂量。通过优化热疗剂量,AuNH-2-Ab同时靶向和消除癌细胞和肿瘤相关巨噬细胞,从而激活有效的抗肿瘤免疫力,而不会受到免疫抑制元件的损害。高温/pH诱导的AuNH-2-Ab的形态转化,涉及表面抗体的分离以抑制原位PD-L1,和内部岩藻依聚糖层的暴露,以激活自然杀伤(NK)细胞。这种精确的光免疫疗法重新编程时间,显著延长小鼠肝细胞癌模型(Hep55.1c)的生存期,并利用单一纳米平台利用ICD生产和检查点抑制剂的协同作用。
    Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.
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  • 文章类型: Journal Article
    内窥镜在人体内导航以观察具有最小侵入性的解剖结构。它们使用的一个主要缺点是它们在大导航过程中的视野窄,中空解剖区域。内窥镜图像的马赛克可以为外科医生提供工具环境的地图。这将有助于程序,提高他们的效率,并可能产生更好的患者结果。磁操纵内窥镜的出现为更安全的程序开辟了道路,并创造了在马赛克地图的生成和该地图内的导航中提供机器人辅助的机会。本文提出了自主导航磁内窥镜的方法,以1)生成内窥镜图像马赛克和2)使用这些马赛克作为用户界面来导航整个探索区域。这些是第一个策略,它允许大型的自主磁导航,微创手术中的中空器官。在双胞胎对双胞胎输血综合征的治疗中,在体外和离体实验中都证明了这些方法的可行性。这种微创手术在子宫内进行,需要在胎盘上凝结双胎的共享血管。脉管系统的马赛克结合自主导航具有显著促进这种挑战性手术的潜力。
    Endoscopes navigate within the human body to observe anatomical structures with minimal invasiveness. A major shortcoming of their use is their narrow field-of-view during navigation in large, hollow anatomical regions. Mosaics of endoscopic images can provide surgeons with a map of the tool\'s environment. This would facilitate procedures, improve their efficiency, and potentially generate better patient outcomes. The emergence of magnetically steered endoscopes opens the way to safer procedures and creates an opportunity to provide robotic assistance both in the generation of the mosaic map and in navigation within this map. This paper proposes methods to autonomously navigate magnetic endoscopes to 1) generate endoscopic image mosaics and 2) use these mosaics as user interfaces to navigate throughout the explored area. These are the first strategies, which allow autonomous magnetic navigation in large, hollow organs during minimally invasive surgeries. The feasibility of these methods is demonstrated experimentally both in vitro and ex vivo in the context of the treatment of twin-to-twin transfusion syndrome. This minimally invasive procedure is performed in utero and necessitates coagulating shared vessels of twin fetuses on the placenta. A mosaic of the vasculature in combination with autonomous navigation has the potential to significantly facilitate this challenging surgery.
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  • 文章类型: Journal Article
    遥控软致动器在包括软机器人在内的许多领域都有很好的潜在应用。探索,和入侵医疗。形状记忆聚合物可以储存和释放能量,导致形状变形,并被认为是制造无绳软机器人的有希望的候选人。在这里,提出了一种基于形状记忆水凝胶的无束缚且无电池的软导航器和夹持器。形状记忆水凝胶是通过明胶和单宁酸之间的氢键作用获得的,基于明胶的氢键和卷曲-三螺旋转变,水凝胶显示出优异的形状记忆性能。此外,引入Fe3O4纳米粒子以赋予水凝胶磁响应性和光热转换能力。最后,在拉伸状态下的形状记忆水凝胶与惰性水凝胶组装以实现双层水凝胶致动器,由于热或光引起的形状记忆层的形状恢复,这可能产生复杂的形状变换。利用磁控制和光响应形状变形,可以通过曲折的路径导航并从难以到达的地方抓取物体的远程可控软夹持器已经完成。这种方法将激发新型形状记忆水凝胶作为远程可控软机器人的设计和制造。
    Remotely controllable soft actuators have promising potential applications in many fields including soft robotics, exploration, and invasion medical treatment. Shape memory polymers could store and release energy, resulting in shape deformation, and have been regarded as promising candidates to fabricate untethered soft robots. Herein, an untethered and battery-free soft navigator and gripper based on a shape memory hydrogel is presented. The shape memory hydrogel is obtained through hydrogen bonding between gelatin and tannic acid, and the hydrogel displays excellent shape memory properties on the basis of hydrogen bonding and the coil-triple helix transition of gelatin. Moreover, Fe3O4 nanoparticles are introduced to endow the hydrogel magnetic responsiveness and photothermal conversion capacity. Finally, the shape memory hydrogel in a stretched state is assembled with an inert hydrogel to achieve a bilayer hydrogel actuator, which could produce complex shape transformation due to the shape recovery of the shape memory layer induced by heat or light. Taking advantage of the magnetically control and light-responsive shape deformation, remotely controllable soft grippers that could navigate through tortuous paths and grasp objects from a hard-to-reach place have been accomplished. This approach will inspire the design and fabrication of novel shape memory hydrogels as remotely controllable soft robots.
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  • 文章类型: Journal Article
    虽然微泡(MB)通常用于超声(US)成像,磁性MB被越来越多地探索,因为它们可以通过施加的磁场梯度被引导到感兴趣的特定位点。这需要调整MB壳组成以延长MB稳定性并提供磁性纳米颗粒的功能化能力。因此,我们开发了由不同分子量的牛血清白蛋白(BSA)和聚L-精氨酸(pArg)的蛋白质-聚合物复合物稳定的充气MB,显示中等分子量分布(15-70kDa)的pArg使MB具有更大的稳定性和声学响应,同时在孵育48小时后保持MB狭窄的直径和THP-1细胞的相对活力。在用超顺磁性氧化铁纳米颗粒(SPION)进行MB功能化后,单个MB提供的磁矩值证实了足够的SPION沉积在BSApArgMB壳上。在用磁镊子模拟体模的血管中以及在具有粘附小鼠肾癌细胞系的培养皿中进行MB磁导航期间,我们证明了通过磁场梯度在所需区域进行磁性MB定位的有效性。进一步利用磁性MB与细胞的共定位来有效地递送装载药物的MB的阿霉素。一起来看,这些发现为控制白蛋白MB特性和SPION负载MB的磁导航开辟了新的途径,这可以设想它们在诊断和治疗需求中的应用。
    While microbubbles (MB) are routinely used for ultrasound (US) imaging, magnetic MB are increasingly explored as they can be guided to specific sites of interest by applied magnetic field gradient. This requires the MB shell composition tuning to prolong MB stability and provide functionalization capabilities with magnetic nanoparticles. Hence, we developed air-filled MB stabilized by a protein-polymer complex of bovine serum albumin (BSA) and poly-L-arginine (pArg) of different molecular weights, showing that pArg of moderate molecular weight distribution (15-70 kDa) enabled MB with greater stability and acoustic response while preserving MB narrow diameters and the relative viability of THP-1 cells after 48 h of incubation. After MB functionalization with superparamagnetic iron oxide nanoparticles (SPION), magnetic moment values provided by single MB confirmed the sufficient SPION deposition onto BSA + pArg MB shells. During MB magnetic navigation in a blood vessel mimicking phantom with magnetic tweezers and in a Petri dish with adherent mouse renal carcinoma cell line, we demonstrated the effectiveness of magnetic MB localization in the desired area by magnetic field gradient. Magnetic MB co-localization with cells was further exploited for effective doxorubicin delivery with drug-loaded MB. Taken together, these findings open new avenues in control over albumin MB properties and magnetic navigation of SPION-loaded MB, which can envisage their applications in diagnostic and therapeutic needs.
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  • 文章类型: Journal Article
    在微创手术中,例如心脏消融,由可变刚度材料制成的磁性转向导管可以实现对人体组织的更高的灵活性和更高的力施加。然而,软状态和刚性状态之间的长过渡时间导致手术持续时间的显著增加。这里,快速反应,描述了多段导管,用于由可变刚度螺纹(FRVST)制成的微创手术,该螺纹封装了螺旋冷却通道。FRVST中的快速刚度变化,由无毒的形状记忆聚合物组成,通过通过螺旋通道泵送水的主动冷却系统来实现。与非冷却版本相比,FRVST显示66倍的刚度变化和26倍的过渡增强。导管允许在80mT外部磁场下在空气中选择性地弯曲每个段高达127°,在水中高达76°。内部工作通道可以用于在手术期间冷却消融尖端,并且用于经由导线或手术工具的部署进行信息交换。
    In minimally invasive surgery, such as cardiac ablation, magnetically steered catheters made of variable-stiffness materials can enable higher dexterity and higher force application to human tissue. However, the long transition time between soft and rigid states leads to a significant increase in procedure duration. Here, a fast-response, multisegmented catheter is described for minimally invasive surgery made of variable-stiffness thread (FRVST) that encapsulates a helical cooling channel. The rapid stiffness change in the FRVST, composed of a nontoxic shape memory polymer, is achieved by an active cooling system that pumps water through the helical channel. The FRVST displays a 66 times stiffness change and a 26 times transition enhancement compare with the noncooled version. The catheter allows for selective bending of each segment up to 127° in air and up to 76° in water under an 80 mT external magnetic field. The inner working channel can be used for cooling an ablation tip during a procedure and for information exchange via the deployment of wires or surgical tools.
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  • 文章类型: Journal Article
    磁控软毫机器人在可编程变形方面取得了重大进展,多式联运运动,在无法到达的地区进行无拘无束的操纵。然而,固有的局限性在固相毫机器人中表现为有限的可变形性,在液相毫机器人中表现为低刚度。在这里,我们提出了一种基于嵌入有磁性纳米颗粒的相变聚合物的三元磁活性微机器人。微型机器人可以在液体中可逆地运输,固体,和粘性流体相通过加热和冷却。液相微型机器人具有弹性变形和移动性,可在受限空间中畅通无阻地导航。粘性流体相millirobot显示出不可逆的变形和大的延展性。固相微型机器人具有良好的形状稳定性和可控的运动能力。此外,三元磁动式微型机器人可以通过相变实现包括刚度变化和形状重构在内的突出功能。机器人可以在复杂的地形中执行潜在的导航功能,三维电路连接,在胃模型中模拟治疗。这种磁动式微型机器人可能会在柔性电子和生物医学中找到新的应用。
    Magnetoactive soft millirobots have made significant advances in programmable deformation, multimodal locomotion, and untethered manipulation in unreachable regions. However, the inherent limitations are manifested in the solid-phase millirobot as limited deformability and in the liquid-phase millirobot as low stiffness. Herein, we propose a ternary-state magnetoactive millirobot based on a phase transitional polymer embedded with magnetic nanoparticles. The millirobot can reversibly transit among the liquid, solid, and viscous-fluid phases through heating and cooling. The liquid-phase millirobot has elastic deformation and mobility for unimpeded navigation in a constrained space. The viscous-fluid phase millirobot shows irreversible deformation and large ductility. The solid-phase millirobot shows good shape stability and controllable locomotion. Moreover, the ternary-state magnetoactive millirobot can achieve prominent capabilities including stiffness change and shape reconfiguration through phase transition. The millirobot can perform potential functions of navigation in complex terrain, three-dimensional circuit connection, and simulated treatment in a stomach model. This magnetoactive millirobot may find new applications in flexible electronics and biomedicine.
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  • 文章类型: Journal Article
    已开发出磁性微型机器人,用于通过远程磁场导航微型环境。然而,有限的推进速度在小尺度仍然是一个问题,在这些装置的可操作性的磁力和扭矩是成正比的,他们的磁性体积。这里,我们提出了一个微型机器人上层结构,which,类似于超分子系统,由两个或更多个微型机器人单元组成,所述微型机器人单元通过物理(瞬时)组件(聚合物框架或线)互连和组织。我们的上层结构由微型制造的磁性螺旋微型机器组成,该机器由含有氧化铁纳米颗粒(IONP)的磁性明胶纳米复合材料互锁。虽然微螺旋使上层建筑运动,IONP用作加热换能器,用于通过磁热疗溶解明胶底盘。在实际演示中,我们用梯度磁场在大通道中展示上层建筑的运动,通过高频交变磁场拆卸上部结构和释放螺旋微机械,以及释放的螺旋通过旋转磁场通过小通道运动。这种适应性强的微型机器人上层结构对不同的磁输入作出反应,可用于在人体复杂的区域内执行复杂的递送程序。本文受版权保护。保留所有权利。
    Magnetic microrobots have been developed for navigating microscale environments by means of remote magnetic fields. However, limited propulsion speeds at small scales remain an issue in the maneuverability of these devices as magnetic force and torque are proportional to their magnetic volume. Here, a microrobotic superstructure is proposed, which, as analogous to a supramolecular system, consists of two or more microrobotic units that are interconnected and organized through a physical (transient) component (a polymeric frame or a thread). The superstructures consist of microfabricated magnetic helical micromachines interlocked by a magnetic gelatin nanocomposite containing iron oxide nanoparticles (IONPs). While the microhelices enable the motion of the superstructure, the IONPs serve as heating transducers for dissolving the gelatin chassis via magnetic hyperthermia. In a practical demonstration, the superstructure\'s motion with a gradient magnetic field in a large channel, the disassembly of the superstructure and release of the helical micromachines by a high-frequency alternating magnetic field, and the corkscrew locomotion of the released helices through a small channel via a rotating magnetic field, is showcased. This adaptable microrobotic superstructure reacts to different magnetic inputs, which can be used to perform complex delivery procedures within intricate regions of the human body.
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  • 文章类型: Journal Article
    由于其广泛的临床应用可能性,磁驱动技术引起了全世界研究人员的注意。设计,执行,在过去的十年中,对磁性导管系统的分析取得了显着进展。本综述的重点是用于导管转向和装置控制的磁性致动。这将在以下各节中详细探讨。讨论了未来的工作和审查系统的挑战,结论最终得到解决。
    Due to their wide range of clinical application possibilities, magnetic actuation technologies have grabbed the attention of researchers worldwide. The design, execution, and analysis of magnetic catheter systems have advanced significantly during the last decade. The review focuses on magnetic actuation for catheter steering and control of the device, which will be explored in detail in the following sections. There is a discussion of future work and the challenges of the review systems, and the conclusions are finally addressed.
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  • 文章类型: Journal Article
    目的:癌症治疗过程中会出现严重的副作用。纳米颗粒的磁驱动是通过提供抗癌药物或增加感染区域的温度来消除这些影响的新方法。出于这个原因,纳米粒子最佳引导的数值模型,通过梯度磁场,在这项研究中介绍了人体动脉系统内部。
    方法:本方法结合计算流体动力学(CFD)和离散元素方法(DEM)技术。此外,通过使用协方差矩阵适应进化策略(CMA-ES)评估每次的最佳磁场强度。在心动周期的五个特征血流速度下,所开发的方法评估和选择最佳的梯度磁场,以消除引导的纳米粒子从预定轨迹的偏差。
    结果:模拟结果表明,在实际条件下,磁性驱动过程中血液流量和纳米载体体积的影响。具体来说,在磁导航过程中,血流量和颗粒体积是成反比的参数。随着血流量的减少,纳米粒子与所需路径的偏差最小化。相反,纳米载体体积的减少增加了颗粒与所述轨迹的距离。然而,随着血流量的增加,需要更大的磁梯度值。此外,所施加的梯度磁值与纳米粒子的位置和血液吹扫速度密切相关。
    结论:根据本研究的结果,导航过程中最重要的参数是粒子的磁性体积。在现实条件下,与导航过程中的颗粒体积相比,血流的影响微不足道。此外,在不同的血流和颗粒体积之间,优化的磁序列存在很大差异。
    OBJECTIVE: Serious side effects are occurred during the cancer therapy. Magnetic driving of nanoparticles is a novel method for the elimination of these effects by supplying with anticancer drug or increase the temperature of the infected area. For this reason, a numerical model for optimal guidance of nanoparticles, through the gradient magnetic field, inside the human artery system is presented in this study.
    METHODS: The present method couples Computational Fluid Dynamics (CFD) and Discrete Element Method (DEM) techniques. In addition, the optimum magnetic intensity each time is evaluated by using the covariance matrix adaptation evolution strategy (CMA-ES). Under five feature blood flow velocities in cardiac cycle, the developed method evaluate and select the optimum gradient magnetic field in order to eliminate the deviation of the guided nanoparticles from a pre-described trajectory.
    RESULTS: Results of the simulations indicate both the influence of the blood flow and the volume of nanocarriers in the magnetic driving process in real conditions. Specifically, the blood flow and the volume of particles are inversely proportional parameters in the magnetic navigation process. As the blood flow is decreased, the deviation of nanoparticles compared to the desired path is minimized. On the contrary, the decrease of the volume of nanocarriers increase the distance of particles from the described trajectory. However, greater magnetic gradient values are needed as the blood flow is increased. Furthermore, the imposed gradient magnetic values are strongly connected with the position of the nanoparticles and the blood blow velocity.
    CONCLUSIONS: Based on the results of the present study, the most important parameter in the navigation process is the magnetic volume of particles. Under real conditions, the effect of the blood flow is insignificant compared to the volume of particles in the navigation process. In addition, great differences in the optimized magnetic sequence are presented both among the different blood flows and the volume of particles.
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  • 文章类型: Journal Article
    未经证实:动脉血栓形成是对人类健康的严重威胁。最近,许多血栓靶向纳米颗粒(NPs)已被构建用于检测血栓或监测溶栓,但其血栓靶向性能有限.考虑到这个缺点,我们设计了一个具有增强血栓靶向能力的特定仿生系统。
    UNASSIGNED:在仿生系统中,选择明胶作为载体,和Fe3O4用作磁导航介质和磁共振(MR)成像剂。CREKA肽,靶向纤维蛋白,与明胶表面缀合以制备靶向NP(TNP),然后被巨噬细胞吞噬以构建仿生系统。在目标站点,仿生系统在低强度聚焦超声(LIFU)照射下释放其内部TNP。此外,偶联的CREKA肽进一步提高了靶向性能。
    未经批准:在这项研究中,我们成功构建了一个仿生系统,并在体外和体内证明了其靶向能力。结果表明,大多数TNP在2W/cm2的LIFU照射下体外10分钟从巨噬细胞中释放。此外,增强的血栓靶向能力,基于巨噬细胞对炎症血栓的自然取向,磁导航和CREKA肽,在离体和体内进行了验证。此外,与仿生系统组相比,TNP组MR图像中肝脏和脾脏信号显著降低,荧光图像中肝脏和脾脏信号显著增强,表明仿生系统比TNP不太可能被网状内皮系统(RES)清除,这可能会促进仿生系统在血栓部位的积累。
    UNASSIGNED:这些结果表明,具有LIFU反应性的磁体引导仿生系统是靶向血栓的优秀候选药物,并有望成为溶栓治疗的创新药物递送系统。
    UNASSIGNED: Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability.
    UNASSIGNED: In the bionic system, gelatin was chosen as a carrier, and Fe3O4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide.
    UNASSIGNED: In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in vivo. Moreover, compared with the bionic system group, the group treated with TNPs had significantly decreased liver and spleen signals in MR images and significantly enhanced liver and spleen signals in fluorescence images, indicating that the bionic system is less likely to be cleared by the reticuloendothelial system (RES) than TNPs, which may promote the accumulation of the bionic system at the site of the thrombus.
    UNASSIGNED: These results suggest that the magnet-guided bionic system with LIFU responsiveness is an excellent candidate for targeting thrombi and holds promise as an innovative drug delivery system for thrombolytic therapy.
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