携抗MUC1单克隆抗体的超声造影剂微泡制备及体外寻靶实验

目的:制备携抗MUCI单克隆抗体的超声造影剂微泡,并评价其体外寻靶能力。方法:采用异型双功能交联剂将小鼠抗MUCI单克隆抗体与超声造影剂微泡相结合,采用激光粒度仪,扫描电镜及激光共聚焦显微镜评价其粒径,形态及结合率。体外培养小鼠EMT6细胞,将其与靶向微泡相混合,激光共聚焦显微镜评价粘附能力。结果:扫描电镜下显示携抗MUCI单克隆抗体造影剂微泡呈规则球体形态,平均粒径2.88±1.34μm,通过异型双功能交联剂,抗MUC1单克隆抗体可结合至超声造影剂微泡表面,其结合率为77.3±10.4%,靶向造影剂粘附体外培养细胞比例为79.2±13.2%。结论:成功制备携抗MUCI的靶向超声造影剂微泡,并且能很好的识别粘附体外培养乳腺癌细胞。     

超声空化强度测量的研究进展

近几十年来,超声波已经广泛应用于生物学和医学领域,在医学领域中超声波可以作为信息载体用于探测人体的病变信息,并且可以用一定剂量的超声波作用于人体病变组织,并通过它对组织的作用达到一定的治疗目的。作为一种无创、非介入性外科技术,它的疗效和安全性越来越被人们所关注。超声波与人体组织的相互作用有三种,分别是机械机制,热学机制,和空化机制。对于机械机制和热机制人们比较熟悉,而对于空化机制则相对陌生。随着超声空化在医学中的应用越来越广泛,其安全性越来越受到人们的关心。要么是其强度迭不到治疗效果,要么是其强度过大损伤人体,因此其强度已成为人们关心的主要主题。本文主要介绍超声空化的主要探讨了几种测量方法及对超声空化有影响的几种参量,并对超声空化的发展进行了展望。     

超声分子成像的研究进展

超声成像无创、无放射性、低成本、实时成像的优点,使其成为目前世界上应用最广的成像手段之一。特别是超声造影剂引入之后,超声成像的图像分辨率和灵敏度得到了大大提高,使超声成像在临床上得到了进一步应用。近年来,随着分子生物学和超声成像技术的不断发展,人们提出了＂超声分子成像＂的概念。它是一项结合了分子靶向造影剂和超声影像技术的能在分子水平下观察病理变化的新兴技术,目前这一技术还处于研究初期阶段。但大量临床前的研究成果已表明超声分子成像在诊断血管生成、炎症和血栓三种疾病具有很大应用前景。本文主要综述了目前常用超声造影剂的种类以及超声分子成像技术的研究现状,并对该技术进行了讨论和展望。     

超声分子成像的研究进展

超声成像无创、无放射性、低成本、实时成像的优点,使其成为目前世界上应用最广的成像手段之一。特别是超声造影剂引入之后,超声成像的图像分辨率和灵敏度得到了大大提高,使超声成像在临床上得到了进一步应用。近年来,随着分子生物学和超声成像技术的不断发展,人们提出了"超声分子成像"的概念。它是一项结合了分子靶向造影剂和超声影像技术的能在分子水平下观察病理变化的新兴技术,目前这一技术还处于研究初期阶段。但大量临床前的研究成果已表明超声分子成像在诊断血管生成、炎症和血栓三种疾病具有很大应用前景。本文主要综述了目前常用超声造影剂的种类以及超声分子成像技术的研究现状,并对该技术进行了讨论和展望。     

超声在植物生理学领域的应用

综述了超声在植物生理学研究和实践中的应用。研究涉及超声对植物体呼吸强度、萌发率、生根状况、某些代谢途径的影响以及超声的空化作用对植物体生理学方面的影响。在植物生理学领域中超声的应用主要是利用了超声的空化作用、机械作用和热效应。     

超声靶向微泡破坏与载药/载基因纳米粒联合应用的生物物理学机制及应用研究进展

超声靶向微泡破坏(ultrasound-targeted microbubble destruction, UTMD)能够安全、高效、简便地递送药物与基因,是当前超声医学领域的研究热点,其机制主要涉及超声辐照微泡引起的空化效应及其二级效应、内吞作用与声辐射力。近年来,随着生物医学材料科学迅猛发展,纳米载药系统取材更加广泛,制备方法愈发精良,载药量日益提高。将纳米载药系统与UTMD进行联合,可以扬长避短,为肿瘤等多种疾病的治疗带来新的思路与希望。本文旨在对UTMD与载药/载基因纳米粒联合应用的生物物理学机制及应用研究进行综述并提出展望。     

超声分子成像：机遇与挑战

随着分子生物学、蛋白组学、基因组学、计算机工程学等学科的不断进步,交叉融合,分子成像逐渐登上历史的舞台,成为研究热点。而超声分子成像随之迅猛发展,近年来超声微泡制备技术的成熟和超声造影检查技术的不断进步,超声造影不再局限获取组织的血流灌注信息,而是逐渐成为特异性的超声分子成像。目前使用超声对比剂研究分子成像和靶向治疗仍处于初级阶段。但是,各种分子成像技术的不断革新和发展,超声分子成像面临着重大的挑战,而在挑战背后同样面临着难逢的机遇。超声医学和分子生物学的迅猛发展,超声分子成像必将成为诊断和治疗疾病的新的手段和方法。超声造影剂仍有许多未能解决的问题,像如何延长微泡的半衰期、如何增强微泡的敏感性和特异性,如何增强目的基因的表达,如何处理组织损伤和高频超声之间的关系等问题,但是如果能解决这些问题,超声造影在现代医学的诊断和治疗中将起到重要的作用。现将超声分子成像综述如下。     

高强度聚焦超声的原理和应用

高强度聚焦超声(High Intensity Focused Ultrasound,简称HIFU)技术是近年来蓬勃发展起来的一种无创外科工具,并已应用于临床的治疗中.该技术的主要生物效应包括:热效应、空化效应和机械效应.该技术的应用已经涉及到肿瘤学、过敏性鼻炎、泌尿学等方面.本文就HIFU技术的应用、现状和前景作以综述.     

超声治疗动脉粥样硬化性心血管疾病研究进展

超声干预治疗动脉粥样硬化性心血管疾病（atherosclerotic cardiovascular disease,ASCVD）是一种非侵入性治疗方法，其应用于临床治疗的前景广阔。超声波在身体组织中产生的机械、空化及生化等一系列作用可以有效清除血管中的斑块或血栓。但是，安全性是超声疗法应用于临床中亟需解决的首要问题。超声波在身体组织中的传播会引起组织损伤。另外，安全处理因超声刺激而产生的斑块或血栓碎片也是超声疗法应用中面临的挑战。除了确保安全性，合理制定治疗方案及治疗参数从而提高超声疗法疗效是超声疗法应用于临床中有待解决的重要问题。本文结合近年来超声干预治疗动脉粥样硬化性心血管疾病方面的各种临床、动物及体外模型实验研究结果，综述了超声干预治疗的机制、不同治疗方法和治疗参数的效果、如何确保安全性，以及提高超声疗法疗效需解决的一系列问题，进而提出可能的解决方案。     

医学超声治疗原理及其临床应用研究

本文从超声波对人体特有的生物效应出发,用生物医学工程的观点,阐述了现代超声治疗技术基本原理及最新临床应用成果,特别是在超声外科治疗技术中的最新发展,展望了超声治疗技术的应用发展前景。     

Tumor cytotoxicity in vivo and radical formation in vitro depend on the shock wave-induced cavitation dose

Local tumor therapy using focused ultrasonic waves may become an important treatment option. This technique exploits the ability of mechanical waves to induce thermal and nonthermal effects noninvasively. The cytotoxicity to cultured cells and biological tissues in vivo that results from exposure to ultrasonic shock waves is considered to be a nonthermal effect that is partly a consequence of ultrasound-induced cavitation. Cavitation is defined as the formation of bubbles during the negative wave cycle; their subsequent oscillation and/or violent implosion can affect surrounding structures. To investigate cavitational effects in cells and tissues, defined cavitation doses must be applied while ideally holding all other potential ultrasound parameters constant. The application of independent cavitation doses has been difficult and has yielded little knowledge about quantitative cavitation-tissue interactions. By using a special shock-wave pulse regimen and laser optical calibration in this study, we were able to control the cavitation dose independently of other physical parameters such as the pressure amplitudes, and averaged acoustic intensity. We treated Dunning prostate tumors (subline R3327-AT1) transplanted into Copenhagen rats with shock waves at three cavitation dose levels and then determined the tumor growth delay and the histopathological changes. All of the treated animals exhibited a significant tumor growth delay compared to the controls. Higher cavitation doses were associated with a greater delay in the growth of the tumor and more severe effects on tumor histopathology, such as hemorrhaging, tissue disruption, and necrosis. In vitro, the cavitation dose level correlated with the amount of radical formation. We concluded that the process of acoustic cavitation was responsible; higher cavitation doses caused greater effects in tumors both in vivo and in vitro. These findings may prove important in local tumor therapy and other applications of ultrasound such as ultrasound-mediated drug delivery.     

The powerful microbubble: from bench to bedside, from intravascular indicator to therapeutic delivery system, and beyond

This review discusses the development, current applications, and therapeutic potential of ultrasound contrast agents. Microbubbles containing gases act as true, intravascular indicators, permitting a noninvasive, quantitative analysis of the spatial and temporal heterogeneity of blood flow and volumes within the microvasculature. These shelled microbubbles are near-perfect reflectors of acoustic ultrasound energy and, when injected intravenously into the bloodstream, reflect ultrasound waves within the capillaries without disrupting the local environment. Accordingly, microbubble ultrasound contrast agents are clinically useful in enhancing ultrasound images and improving the accuracy of diagnoses. More recently, ultrasound contrast agents have been used to directly visualize the vasa vasorum and neovascularization of atherosclerotic carotid artery plaques, thus suggesting a new paradigm for diagnosis and treatment of atherosclerosis. Future applications of these microscopic agents include the deliver of site-specific therapy to targeted organs in the body. Medical therapies may use these microbubbles as carriers for newer therapeutic options.     

Tailoring the size distribution of ultrasound contrast agents: possible method for improving sensitivity in molecular imaging

Encapsulated microbubble contrast agents incorporating an adhesion ligand in the microbubble shell are used for molecular imaging with ultrasound. Currently available microbubble agents are produced with techniques that result in a large size variance. Detection of these contrast agents depends on properties related to the microbubble diameter such as resonant frequency, and current ultrasound imaging systems have bandwidth limits that reduce their sensitivity to a polydisperse contrast agent population. For ultrasonic molecular imaging, in which only a limited number of targeted contrast agents may be retained at the site of pathology, it is important to optimize the sensitivity of the imaging system to the entire population of contrast agent. This article presents contrast agents with a narrow size distribution that are targeted for molecular imaging applications. The production of a functionalized, lipid-encapsulated, microbubble contrast agent with a monodisperse population is demonstrated, and we evaluate parameters that influence the size distribution and demonstrate initial acoustic testing.     

Overview of experimental studies of biological effects of medical ultrasound caused by gas body activation and inertial cavitation

Ultrasound exposure can induce bioeffects in mammalian tissue by the nonthermal mechanism of gas body activation. Pre-existing bodies of gas may be activated even at low-pressure amplitudes. At higher-pressure amplitudes, violent cavitation activity with inertial collapse of microbubbles can be generated from latent nucleation sites or from the destabilization of gas bodies. Mechanical perturbation at the activation sites leads to biological effects on nearby cells and structures. Shockwave lithotripsy was the first medical ultrasound application for which significant cavitational bioeffects were demonstrated in mammalian tissues, including hemorrhage and injury in the kidney. Lithotripter shockwaves can also cause hemorrhage in lung and intestine by activation of pre-existing gas bodies in these tissues. Modern diagnostic ultrasound equipment develops pressure amplitudes sufficient for inertial cavitation, but the living body normally lacks suitable cavitation nuclei. Ultrasound contrast agents (UCAs) are suspensions of microscopic gas bodies created to enhance the echogenicity of blood. Ultrasound contrast agent gas bodies also provide nuclei for inertial cavitation. Bioeffects from contrast-aided diagnostic ultrasound depend on pressure amplitude, UCA dose, dosage delivery method and image timing parameters. Microvascular leakage, capillary rupture, cardiomyocyte killing, inflammatory cell infiltration, and premature ventricular contractions have been reported for myocardial contrast echocardiography with clinical ultrasound machines and clinically relevant agent doses in laboratory animals. Similar bioeffects have been reported in intestine, skeletal muscle, fat, lymph nodes and kidney. These microscale bioeffects could be induced unknowingly in diagnostic examinations; however, the medical significance of bioeffects of diagnostic ultrasound with contrast agents is not yet fully understood in relation to the clinical setting.     

Inhibition of barnacle cyprid settlement using low frequency and intensity ultrasound

Low frequency, low intensity ultrasound was demonstrated as an effective inhibitor of barnacle cyprid settlement. When the same substratum vibration amplitude (10.05 nm) and acoustic pressure (5 kPa) were applied, ultrasound at a frequency of 23?kHz significantly reduced cyprid settlement. The mechanism appeared to differ from the ultrasonic cavitation induced inhibition previously reported as no increased mortality was observed, and no change in the exploratory behaviour of cyprids was observed when they were exposed to this continuous ultrasonic irradiation regime. The application of ultrasound treatment in an intermittent mode of '5?min on and 20?min off' at 20-25?kHz and at the low intensity of 5?kPa produced the same effect as the continuous application of 23?kHz. This energy efficient approach to the use of low frequency, low intensity ultrasound may present a promising and efficient strategy regarding irradiation treatment for antifouling applications.     

Ultrasound: mechanical gene transfer into plant cells by sonoporation

Development of nonviral gene transfer methods would be a valuable alternative of gene therapy or transformation. Ultrasound can produce a variety of nonthermal bioeffects via acoustic cavitation. Cavitation bubbles can induce cell death or transient membrane permeabilization (sonoporation) on cells. Application of sonoporation for gene transfer into cells or tissues develops quickly in recent years. Many studies have been performed in vitro exposure systems to a variety of cell lines transfected successfully. In vivo, cavitation initiation and control are more difficult, but can be enhanced by ultrasound contrast agents (microbubbles). The use of ultrasound for nonviral gene delivery has been applied for mammalian systems, which provides a fundamental basis and strong promise for development of new gene therapy methods for clinical medicine. In this paper, ultrasound applied to plant cell transformation or gene transfer is reviewed. Recently, most researches are focused on sonication-assisted Agrobacterium-mediated transformation (SAAT) in plant cells or tissues. Microbubbles are also proposed to apply to gene transfer in plant cells and tissues.     

Ultrasound-Targeted Microbubble Destruction (UTMD) for Localized Drug Delivery into Tumor Tissue

Background

Ultrasound-targeted microbubble destruction (UTMD) is a type of ultrasound therapy, in which low frequency moderate power ultrasound is combined with microbubbles to trigger cavitation. Cavitation is the process of oscillation of gas bubbles causing biophysical effects such as pushing and pulling or shock waves that permeabilize biological barriers. In vivo, cavitation results in tissue permeabilization and is used to enable local delivery of nanomedicine. While cavitation can occur in biological liquids when high pressure ultrasound is applied, the use of microbubbles as cavitation nuclei in UTMD largely facilitates the induction of cavitation. UTMD is intensively studied for drug delivery into tumor tissue, but also for the activation of anti-tumor immune responses. The first clinical studies of UTMD-mediated chemotherapy delivery confirmed safety and efficacy of this approach.