自建光声超声双模态成像系统的肿瘤成像分析

现有B超成像可以提供基于声阻抗差异的组织解剖结构信息,而近年来研究发现,光声成像可以提供标记组织成分的分布和功能信息。本文基于商用B超仪和脉冲激光系统建立了光声超声双模态成像系统,实现了超声组织结构成像和光声生物功能的同时成像。首先基于血红蛋白在某些波段的较强吸光性,实现了肿瘤内部组织血管灌注图像;其次用链接有靶向抗体的纳米颗粒作为靶向光声造影剂,对恶性肿瘤边缘和内部的血管以及血管附近的肿瘤组织进行了成像。最终,通过超声和光声的融合图像提供的肿瘤结构信息与光声图像提供的肿瘤功能信息,可以准确识别肿瘤组织。     

卟啉纳米技术:探索生物光子学新视角

我们最新发现了卟啉纳米,第一种集多种功能与优良光学特性于一身、全部有机的纳米颗粒。这种纳米颗粒通过卟啉脂质自组装形成一个约100nm的类脂质体结构,该颗粒上极高的卟啉密度(>80 000每颗粒)使其能够高效吸收光能并转换成热能,成为理想的光热治疗以及光声成像的载体,也能够进行荧光成像以及光动力治疗。此外,卟啉纳米也可通过螯合金属离子进行PET和MRI成像。通过改变卟啉脂质组装,开发了一系列不同尺寸和生物光学功能的卟啉纳米和微米颗粒,如卟啉纳米碟、卟啉纳米微泡、卟啉微反应器、卟啉-金纳米颗粒等。有别于传统"搭积木"式的多功能纳米载体,卟啉纳米内在的多功能特性和超简单的结构代表了一种全新的纳米颗粒设计概念,具有临床转化的前景。     

用基于声类比的边界元计算管道风扇的管道声传播和辐射

本文介绍了用基于声类比的边界元计算管道风扇声场的新方法,将已被成功地应用于物体对外声场的散射计算方法推广应用到管道风扇的管内声传播和管口声辐射问题。数值结果表明了模型和方法的正确性及其可以作为管道声处理降噪敏果预测的工具。     

基于NMR的4T1荷瘤小鼠脾脏受不同给药方式影响的代谢组学研究

联合阿霉素和紫杉醇治疗肿瘤的策略在临床上已有广泛应用,为了进一步借助纳米载体对肿瘤组织的靶向优势,以良好生物相容性纳米载体包埋阿霉素和紫杉醇的新型给药方式得以发展.虽然前期研究结果显示纳米给药方式相对传统给药治疗有更好的抑制肿瘤生长的效果,但是它们在分子代谢水平对机体的影响并没有被确切研究.本文采用4T1荷瘤乳腺癌模型小鼠,通过比较荷瘤小鼠分别在不处理、传统给药方式和通过纳米载体给药处理的条件下与健康小鼠脾脏代谢组的差异,发现传统给药处理对小鼠肠道微生物相关的代谢紊乱有较好的恢复效果,而通过纳米载体的给药处理可以更好的调节荷瘤小鼠的葡萄糖和延胡索酸等与能量供应相关的代谢途径.此外,这两种给药方式都不能有效改善荷瘤小鼠显著的脾脏肿大症状,也不能改善脾脏免疫调节功能和供应肿瘤生长而导致的氨基酸、有机酸、核酸和胆碱等一系列代谢物变化.这可能与脾脏对外来肿瘤的免疫反应较为激烈而有效药物治疗时间较短有关.该研究为更全面认识荷瘤小鼠脾脏代谢表型变化和不同给药方式对脾脏代谢组的影响提供了基础数据.     

基于相干光时域反射型的光纤分布式声增敏传感研究

开展了基于相干光时域反射型的光纤分布式声增敏传感研究,提出了单端固定开口波纹薄筒光纤声增敏方法,建立了光纤声增敏装置波节间距、单波节轴向刚度、光纤长度等参数对光纤相位灵敏度的影响理论模型.制作了3种规格的光纤声增敏传感装置进行声传感实验.实验结果表明,声增敏传感装置相位灵敏度达到2.975 rad/Pa,最小声探测信号达到60.1 dB,3种规格的声增敏传感装置的灵敏度测试值与理论分析基本一致.研究结果为高灵敏度的光纤分布式声传感的进一步发展提供了理论和实验基础.     

感声微液滴气化的物理机制新发现

正感声的微小乳液液滴(其成分多为全氟碳化物,Perfluorocarbon),因其较低的沸点,可以通过体外的超声激励而实现液态-气态的状态转化,即气化。这种感声的乳液液滴可以成为包裹药物的载体实现超声激发的靶向药物释放;可以实现靶向超声造影成像;也可以用于栓塞疗法治疗肿瘤等。因感声乳液液滴在医学诊断和治疗方面具有广泛的应用潜力,成为医学超声领域的研究热点。然而,感声微液滴气化的物理机制尚不清楚。目前在实     

Au纳米颗粒负载WO_3纳米花复合结构的二甲苯气敏性能

本文采用水热法成功制备了Au纳米颗粒负载的WO_3纳米花材料,并运用XRD,SEM,TEM等手段对其晶体结构和形貌进行了表征,并详细研究了其对二甲苯的气敏性能.首先对Au的浓度和气敏元件的工作温度进行了优化,结果表明,0.4μl Au纳米颗粒负载的WO_3对二甲苯的灵敏度最高,最佳工作温度为250℃.同纯WO_3相比,Au纳米颗粒负载的WO_3纳米花具有更快的响应/恢复速度和更高的目标气体选择性,在100 ppm二甲苯中灵敏度达到了29.5.此外,检测限度可以低至5 ppm水平.最后对气敏元件表面可能发生的氧化还原反应的机理进行了研究和讨论,认为Au负载的WO_3纳米花材料有望应用于二甲苯气体传感器.     

声动力学疗法治疗肿瘤的研究现状及前景

由于光在人体组织中穿透能力差，光动力学疗法治疗肿瘤主要集中在人体表面浅层部位，为了克服光动力学疗法治疗肿瘤的局限性，利用超声激活血卟啉进行抗肿瘤效应（即声动力学疗法）已成为近几年国内外研究者关注的热点之一。文章就声动力学疗法治疗肿瘤的研究现状、研究方法、实验结果以及作用机理进行了扼要综述，分析了阻碍声动力学疗法临床应用存在的问题，并对问题的解决和未来发展趋势提出了自己的见解。     

高频高灵敏光声探头的光声内窥成像

光声内窥成像技术具有高分辨、高精准、功能成像等优点,是目前临床新型成像诊断技术研究的热点。然而,光声内窥成像技术受激光器安全能量阈值和光声换能器灵敏度的制约,现有的光声内窥成像技术大多无法兼顾高成像信噪比和小尺寸要求。为了解决光声信号回波能量低、光声图像信噪比差的问题,该文采用一种带有集成前端放大器的小尺寸的光声探头设计方案,其中心频率达到30 MHz,直径小于2.5 mm,通过仿体实验证明其仿体中的成像深度可达6.5 mm,横向成像分辨率可达144.9μm,纵向分辨率为111.1μm,尤其是,成像信噪比相较于对照组的传统光声换能器提高了11.5 dB。该文研究表明,前端集成放大光声探头能有效提高光声成像信噪比,改善成像质量,为提高光声内窥临床诊断精准度提供了新方法。     

基于二硫化钼的可调一维声子晶体

声子晶体所具有的负折射率、 局域缺陷态与弹性波带隙等特性, 使其在声学隐身、 声学波导以及减震降噪等方向展现了巨大的潜力. 同时, 二硫化钼优异的电学和力学性能使其成为制备纳米机电器件的理想材料. 将单层二硫化钼转移到预先图案化的周期性结构上, 可以制备出纳米尺度的声子晶体器件. 本文设计了一种通过将单层二硫化钼转移贴合在预先制备的周期性沟槽阵列上, 形成一维声子晶体的方案. 有限元分析表明, 这种声子晶体在MHz 范围存在声子能带结构, 可以实现对声波传播的控制. 我们可以通过改变结构参数, 或者通过改变施加在栅电极上的电压, 对能带进行调控. 这种结构为开发基于二维材料的纳米尺度的声子晶体器件提供了可能性.     

Nanosonosensitization by Using Copper–Cysteamine Nanoparticles Augmented Sonodynamic Cancer Treatment

Sonodynamic therapy (SDT), as a newly emerging and promising modality for cancer treatment, has been extensively investigated but with limited therapeutic outcome because of the absence of highly efficient sonosensitizer. Copper–cysteamine (Cu–Cy), as a new sensitizer, has been reported for oxidative therapy which can be activated with light, X‐ray, or microwave. Herein, for the first time, Cu–Cy nanoparticles are reported as new sonosensitizers for SDT on breast cancer treatment. Upon exposure of Cu–Cy nanoparticles to ultrasound, a large quantity of reactive oxygen species (ROS) are generated for cancer cell destruction with a high SDT efficiency to induce cell apoptosis and necrosis as observed in vitro. In vivo animal studies show a significant inhibition of tumor growth for the xenografts of 4T1 cancer cells with the combination of 0.75 mg kg⁻¹ Cu–Cy and ultrasound. Overall, the preliminary results show that Cu–Cy nanoparticles can significantly augment the levels of ROS induced by ultrasound, demonstrating Cu–Cy is a new kind of efficient sonosensitzers for SDT applications. Such therapeutic platform by integrating a noninvasive, highly safe, deep‐penetration ultrasound modality. and quickly developed versatile nanosensitizers for tumor eradication will facilitate SDT future clinical translation.     

Oxygen-carrying biomimetic nanoplatform for sonodynamic killing of bacteria and treatment of infection diseases

Among various novel antimicrobial therapies, sonodynamic therapy (SDT) exhibits its advantages for the treatment of bacterial infections due to its high penetration depth and low side effects. In this study, a new nanosonosensitizer (HFH@ZIF-8) that loads sonosensitizer hematoporphyrin monomethyl ether (HMME) into zeolitic imidazolate framework-8 (ZIF-8), was constructed for killing multidrug-resistant (MDR) bacteria and treatment of in vivo infection diseases by SDT. In particular, the developed HFH@ZIF-8 exhibited enhanced water-solubility, good biocompatibility, and improved disease-targeting capability for delivering and releasing HMME and ablating the infected lesion. More importantly, the presence of oxygen-carrying hemoglobin for HFH@ZIF-8 can offer sufficient oxygen consumption by SDT, augmenting the efficacy of SDT by improving ROS generating efficiency against deep tissue multidrug-resistant bacterial infection. Therefore, this study paves a new avenue for treating infection disease, particularly for antibiotic resistant bacterial infection.     

Combination of sonodynamic with temozolomide inhibits C6 glioma migration and promotes mitochondrial pathway apoptosis via suppressing NHE-1 expression

Temozolomide (TMZ) was used for clinical postoperative or non-surgical chemotherapy patients. However, its effect remains unsatisfactory and gradually discovered that the presence of chemoresistance. To explore more effective therapy using TMZ, we investigate the effects of combination of application of TMZ together with Sonodynamic therapy (SDT), which is based on the ultrasonic activation of a sonosensitizer, with low toxicity, noninvasive, deeper penetrability and a promising approach for treating malignant glioma by inducing apoptosis on glioma cells in vitro. Sodium–hydrogen exchanger isoform 1 (NHE1), which enable glioblastoma cells to escape TMZ-mediated toxicity via increased H⁺ extrusion and affect the apoptosis effect on C6 glioma cells in vitro. The C6 cells survival rate and time point of TMZ resistance were tested by the Cell Counting Kit-8 (CCK8) viability assay. Western blot analysis results showed that the expression of NHE1 and matrix metalloproteinase-2 (MMP-2) protein obviously decreased by TMZ + SDT. Meanwhile, combined treatments enhanced the expression of mitochondrial pathway apoptosis proteins, as well as suppressed MMP-2 to weaken the migration ability in TMZ-resistant C6 cell line. These results provided the first evidence that the sensitivity of TMZ chemotherapy in resistant malignant glioma may be improved by SDT.     

Enhanced sonodynamic therapy by carbon dots-shelled microbubbles with focused ultrasound

Sonodynamic therapy involving the non-invasive and local generation of lethal reactive oxygen species (ROS) via ultrasound (US) with sonosensitizers has been proposed as an emerging tumor therapy strategy. However, such therapy is usually associated with inertial cavitation and unnecessary damage to healthy tissue because current sonosensitizers have insufficient sensitivity to US. Here, we report the use of a new proposed sonosensitizer, carbon dots (C-dots), to assemble microbubbles with a gas core (C-dots MBs). As the C-dots were directly integrated into the MB shell, they could effectively absorb the energy of inertial cavitation and transfer it to ROS. Our results revealed the appearance of ¹O₂, •OH, and H₂O₂ after US irradiation of C-dots MBs. In in vitro experiments, treatment with C-dots MBs plus US induced lipid peroxidation, elevation of intracellular ROS, and apoptosis in 32.5%, 45.3%, and 50.1% of cells respectively. In an animal solid tumor model, treatment with C-dots MBs plus US resulted in a 3-fold and 2.5-fold increase in the proportion of ROS-damaged cells and apoptotic cells, respectively, compared to C-dots MBs alone. These results will pave the way for the design of novel multifunctional sonosensitizers for SDT tumor therapy.     

Bleomycin enhances the efficacy of sonodynamic therapy using aluminum phthalocyanine disulfonate

Sonodynamic therapy (SDT), or ultrasound combined with sonosensitization, is a promising approach because it is noninvasive and penetrates deeper than light does in photodynamic therapy. We examined whether bleomycin (BLM) could improve the efficacy of SDT. We performed an in vitro study using Colon-26 cells, which are derived from mouse colon cancer. SDT with BLM was significantly more cytotoxic than SDT alone both in vitro and in vivo. We also observed an ultrasound intensity-dependent cytotoxic effect of SDT with BLM. These findings suggest that SDT with BLM might provide a novel noninvasive treatment for deep-seated tumors.     

Sonodynamic therapy--a review of the synergistic effects of drugs and ultrasound

Sonodynamic therapy, the ultrasound dependent enhancement of cytotoxic activities of certain compounds (sonosensitizers) in studies with cells in vitro and in tumor bearing animals, is reviewed. The attractive features of this modality for cancer treatment emerges from the ability to focus the ultrasound energy on malignancy sites buried deep in tissues and to locally activate a preloaded sonosensitizer. Possible mechanisms of sonodynamic therapy include generation of sonosensitizer derived radicals which initiate chain peroxidation of membrane lipids via peroxyl and/or alkoxyl radicals, the physical destabilization of the cell membrane by the sonosensitizer thereby rendering the cell more susceptible to shear forces or ultrasound enhanced drug transport across the cell membrane (sonoporation). Evidence against the role of singlet oxygen in sonodynamic therapy is discussed. The mechanism of sonodynamic therapy is probably not governed by a universal mechanism, but may be influenced by multiple factors including the nature of the biological model, the sonosensitizer and the ultrasound parameters. The current review emphasizes the effect of ultrasound induced free radicals in sonodynamic therapy.     

Narrative review: Diabetic foot and infrared thermography

Diabetic foot is one of the major complications experienced by diabetic patients. An early identification and appropriate treatment of diabetic foot problems can prevent devastating consequences such as limb amputation. Several studies have demonstrated that temperature variations in the plantar region can be related to diabetic foot problems. Infrared thermography has been successfully used to detect complication related to diabetic foot, mainly because it is presented as a rapid, non-contact and non-invasive technique to visualize the temperature distribution of the feet. In this review, an overview of studies that relate foot temperature with diabetic foot problems through infrared thermography is presented. Through this research, it can be appreciated the potential of infrared thermography and the benefits that this technique present in this application. This paper also presents the different methods for thermogram analysis and the advantages and disadvantages of each one, being the asymmetric analysis the method most used so far.     

细胞膜伪装的纳米载体用于光热治疗的研究进展

纳米载体一直是肿瘤精准治疗的重要研究领域。其中以细胞膜伪装的纳米药物载体作为一种新颖的药物载体平台,在近年来已成为药物传递领域的研究热点。本文综述了不同种类细胞膜伪装的纳米载体应用于光热治疗的最新进展。将细胞膜与纳米材料结合起来,可进一步推进纳米载体的研究,这将对相关领域的发展产生重要影响。     

Apoptosis induced by sonodynamic treatment by protoporphyrin IX on MDA-MB-231 cells

Sonodynamic therapy (SDT) is a promising modality for cancer treatment, involving the synergistic interaction of ultrasound and some chemical compounds termed as sono-sensitizers. It has been found that SDT can lead to apoptotic cell death because of the induction of direct sonochemical and subsequent redox reactions. However, the detailed mechanisms are not clear. This study was to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX (PpIX) on MDA-MB-231 cells. The fluorescence microscope was used to detect the sub-cellular localization of PpIX. Several distinct sonochemical effects were found after SDT treatment, including the decrease of cell viability, generation of intracellular ROS, the loss of mitochondrial membrane potential. The activation of some special apoptosis-associated proteins [Caspase-9, Caspase-3 and polypeptide poly (ADP-robose) polymerase] was evaluated by western blotting. The results show that PpIX mediated SDT (PpIX-SDT) treatment could obviously inhibit the proliferation of MDA-MB-231 cells, and which was significantly reduced by the pan-Caspase inhibitor z-VAD-fmk and the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC). Further, SDT induced a conspicuous loss of mitochondrial membrane potential (MMP) and a mass of ROS accumulation in MDA-MB-231 cells at 1 h post-treatment and the SDT-treated cells showed obvious Caspase-3 and Caspase-9 activation, and PARP cleavage at 6 h after treatment. And, the general apoptosis marker-Caspase-3 activation-was also greatly relieved by NAC. These findings primarily indicate a Caspase-depended apoptosis could be induced by PpIX-SDT in MDA-MB-231 cells, and the intracellular ROS was involved during the apoptotic process.     

Damage effects of protoporphyrin IX - sonodynamic therapy on the cytoskeletal F-actin of Ehrlich ascites carcinoma cells

In this study, we report evidence of the damage effects of sonodynamic therapy (SDT) on a novel intracellular target, cytoskeletal F-actin, that has great importance for cancer treatment. Ehrlich ascites carcinoma (EAC) cells suspended in PBS were exposed to ultrasound at 1.34MHz for up to 60s in the presence and absence of protoporphyrin IX (PPIX). To evaluate the polymeric state and distribution of actin filaments (AF) we employed FITC-Phalloidin staining. The percentage of cells with intact AF was decreased with 10-80muMu PPIX after ultrasonic exposure, while only few cells with disturbed F-actin were observed with 80muMu PPIX alone. The fluorescence intensity of FITC-Phalloidin labeled cells was detected by flow cytometry. The morphological changes of EAC cells were observed by scanning electron microscope (SEM). The nuclei were stained with Hoechst 33258 to determine apoptosis. Cytoskeletal F-actin and cell morphological changes were dependent on the time after SDT. Some cells suffered deformations of plasma membrane as blebs that reacted positively to FITC-Phalloidin at 2h after SDT treatment. Many of the cells showed the typically apoptotic chromatin fragmentation. The alterations were more significant 4h later. Our results showed that cytoskeletal F-actin might represent an important target for the SDT treatment and the observed effect on F-actin and the subsequent bleb formation mainly due to apoptosis formation due to the treatment.