纳米粒子有望诊疗心血管病

胆固醇有“好”与“坏”之分,“好”胆固醇是高密度脂蛋白,可以把血液中游离胆固醇运送到肝脏后排泄掉,而“坏”胆固醇是低密度脂蛋白,会积存在血管壁上,时间长了容易引起血管硬化,导致中风或心肌梗塞。     

纳米粒子在口服胰岛素制剂中的应用研究

由于胰岛素作为一种蛋白质药物,易被胃肠道中的消化酶降解,降低胰岛素的生物利用度。近年来各种口服胰岛素制剂被开发研究,其中纳米粒子在改善口服胰岛素生物利用度,提高降血糖作用方面具有一定的优势。文中将纳米粒子分为合成高分子材料纳米粒子、天然高分子材料纳米粒子和其他类型纳米粒子,分别从各类纳米粒子特点、生物相容性、体内降血糖效果以及生物利用度等体内体外性能研究方面,对其在口服胰岛素制剂中的应用进行简述。     

纳米涂料的应用及发展建议

详细介绍了纳米粒子在耐老化、抗静电、隐身、抗菌杀菌等涂料中的原理和应用 ,指出了纳米涂料研究中存在的主要问题 ,并对我国纳米涂料的发展提出建议。     

Ａg纳米颗粒与纳米结构薄膜的研究进展

介绍了 Ag纳米颗粒与纳米结构薄膜的研究概况、制备和表征方法,并展望了 Ag纳米颗粒在纳米电子学方面的潜在应用前景。     

纳米粒子的新应用--纳米润滑添加剂的发展现状

总结了当前用于润滑油领域的纳米添加剂的类型、所能达到的润滑效果以及在摩擦过程中起抗磨性的原理。特别介绍了纳米氢氧化物、纳米硼酸盐等的润滑性能。叙述了纳米粒子及其抗磨性的检测手段 ,并概括了纳米润滑添加剂的制备方法及应用前景     

纳米镍/聚苯胺复合粒子的制备与表征

采用对氨基苯甲酸（ABA）处理纳米镍粉,然后在ABA-nano-Ni（ABA处理的纳米镍粉）的存在下苯胺（An）原位化学氧化聚合,形成纳米镍/聚苯胺（PANi/nano-Ni）复合粒子.IR和TGA分析表明ABA通过化学键与纳米镍粒子结合,颗粒表面引入了-NH2基团;采用IR、UV、DSC、TEM等分析手段对复合粒子PANi/nano-Ni进行了分析表征.结果表明苯胺在ABA-nano-Ni表面进行聚合,纳米镍粉表面的NH2基团参与了聚合反应,形成了具有核壳结构的复合粒子.     

基于无机纳米粒子模板刻蚀的纳米阵列

阐述了利用不同的方法,如自组装、嵌段共聚物辅助等方法在基底表面形成一层均匀的无机材料纳米粒子掩模,以此作为模板进行刻蚀,可得到各种纳米图形和纳米结构。这一方法具有操作简单、成本低、可批量生产等优点,在纳米电子器件等领域具有广泛的应用前景。     

纳米纤维素/银纳米粒子的制备和表征

以纳米纤维素(NCC)为分散剂,硼氢化钠为还原剂还原硝酸银,化学还原法制备纳米纤维素/银纳米粒子。m(Ag)/m(NCC)=5%制备的纳米纤维素/银纳米粒子,X射线衍射分析结果表明,纳米纤维素/银纳米粒子中NCC和银纳米粒子相互混合并未改变各自的晶型,纳米纤维素/银纳米粒子中银纳米粒子的晶粒尺寸为11.87nm,与透射电子显微镜(TEM)所测银纳米粒子直径(10nm)相近;热重分析结果表明,纳米纤维素/银纳米粒子的热稳定性较纳米纤维素稍有下降。透射电子显微镜(TEM)分析、紫外光谱分析、固含量分析、机理分析和抑菌活性分析结果表明,m(Ag)/m(NCC)=3%时制备的纳米纤维素/银纳米粒子对大肠杆菌和金黄色葡萄球菌均有抑制作用,且银纳米粒子在纳米纤维素/银纳米粒子中分散较均匀。     

纳米纤维素负载金属纳米粒子复合材料的研究进展

纳米纤维素以其独特的形态特征,优异的机械强度、生物相容性和生物降解性在纳米材料领域得到了广泛的应用.其高比表面积和丰富的活性表面基团可以通过多种物理或化学方法负载纳米金属粒子,为此,综述了银、金、铜和氧化锌等纳米金属粒子在纳米纤维素上的负载方法,并介绍了此类复合材料在抗菌材料、传感器和催化剂等领域的应用.     

多功能介孔氧化硅基纳米诊疗剂的研究进展

无机介孔纳米生物材料在药物靶向输送、组织工程、基因传输治疗、分子影像、无创手术增效治疗等医学领域具有广阔的应用前景, 对于诸如癌症等重大疾病的早期诊断与高效治疗具有重要的意义。本文以医学应用需求为背景, 以纳米合成化学为基础, 从多功能介孔纳米生物材料的设计入手, 结合本课题组的研究进展, 综述了介孔基纳米诊疗剂的研究现状和未来发展的趋势。通过对介孔SiO₂纳米粒子进行功能化修饰, 赋予其特定的功能, 不仅可以作为临床分子影像(核磁共振成像、荧光成像以及各种成像模式的复合)的造影剂对疾病进行诊断, 并能同时高效地包覆和传输药物对疾病进行治疗(化疗、基因治疗、光动力学治疗或者无创手术治疗)。随着纳米生物技术的发展和纳米合成化学的进步, 设计和制备具有特定功能的满足临床需求的介孔氧化硅基纳米生物材料, 并系统地评价其细胞生物学效应和生物安全性, 将会真正实现其在临床上的应用, 从而造福人类。     

Redox Responsive Metal Organic Framework Nanoparticles Induces Ferroptosis for Cancer Therapy

Ferroptosis is attracting significant attention due to its effectiveness in tumor treatment. The efficiency to produce toxic lipid peroxides (LPOs) at the tumor site plays a key role in ferroptosis. A hybrid PFP@Fe/Cu‐SS metal organic framework (MOF) is synthesized and shown to increase intratumoral LPO content through redox reactions generating ·OH. In addition, glutathione (GSH) depletion through disulfide‐thiol exchange leads to the inactivation of glutathione peroxide 4 (GPX4), which results in a further increase in LPO content. This MOF exhibits high inhibitory effect on the growth of xenografted Huh‐7 tumors in mice. The coadministration of a ferroptosis inhibitor reduces the antitumor effect of the MOF, leading to a restoration of GPX4 activity and an increase in tumor growth. Moreover, the construction of Cu into mesoporous PFP@Fe/Cu‐SS not only allows the MOF to be used as a contrast agent for T₁‐weighted magnetic resonance imaging, but also renders its photothermal conversion capacity. Thus, near‐infrared irradiation is able to induce photothermal therapy and transform the encapsulated liquid perfluoropentane into microbubbles for ultrasound imaging.     

Development of Novel Tumor‐Targeted Theranostic Nanoparticles Activated by Membrane‐Type Matrix Metalloproteinases for Combined Cancer Magnetic Resonance Imaging and Therapy

A major drawback with current cancer therapy is the prevalence of unrequired dose‐limiting toxicity to non‐cancerous tissues and organs, which is further compounded by a limited ability to rapidly and easily monitor drug delivery, pharmacodynamics and therapeutic response. In this report, the design and characterization of novel multifunctional “theranostic” nanoparticles (TNPs) is described for enzyme‐specific drug activation at tumor sites and simultaneous in vivo magnetic resonance imaging (MRI) of drug delivery. TNPs are synthesized by conjugation of FDA‐approved iron oxide nanoparticles ferumoxytol to an MMP‐activatable peptide conjugate of azademethylcolchicine (ICT), creating CLIO‐ICTs (TNPs). Significant cell death is observed in TNP‐treated MMP‐14 positive MMTV‐PyMT breast cancer cells in vitro, but not MMP‐14 negative fibroblasts or cells treated with ferumoxytol alone. Intravenous administration of TNPs to MMTV‐PyMT tumor‐bearing mice and subsequent MRI demonstrates significant tumor selective accumulation of the TNP, an observation confirmed by histopathology. Treatment with CLIO‐ICTs induces a significant antitumor effect and tumor necrosis, a response not observed with ferumoxytol. Furthermore, no toxicity or cell death is observed in normal tissues following treatment with CLIO‐ICTs, ICT, or ferumoxytol. These findings demonstrate proof of concept for a new nanotemplate that integrates tumor specificity, drug delivery and in vivo imaging into a single TNP entity through attachment of enzyme‐activated prodrugs onto magnetic nanoparticles. This novel approach holds the potential to significantly improve targeted cancer therapies, and ultimately enable personalized therapy regimens.     

A Versatile Theranostic Nanoplatform with Aggregation-Induced Emission Properties: Fluorescence Monitoring,Cellular Organelle Targeting,and Image-Guided Photodynamic Therapy

Photosensitizers (PSs) play a key role in the photodynamic therapy (PDT) of tumors. However, commonly used PSs are prone to intrinsic fluorescence aggregation-caused quenching and photobleaching; this drawback severely limits the clinical application of PDT, necessitating new phototheranostic agents. Herein, a multifunctional theranostic nanoplatform (named TTCBTA NP) is designed and constructed to achieve fluorescence monitoring, lysosome-specific targeting, and image-guided PDT. TTCBTA with a twisted conformation and D-A structure is encapsulated in amphiphilic Pluronic F127 to form nanoparticles (NPs) in ultrapure water. The NPs exhibit biocompatibility, high stability, strong near-infrared emission, and desirable reactive oxygen species (ROSs) production capacity. The TTCBTA NPs also show high-efficiency photo-damage, negligible dark toxicity, excellent fluorescent tracing, and high accumulation in lysosome for tumor cells. Furthermore, TTCBTA NPs are used to obtain fluorescence images with good resolution of MCF-7 tumors in xenografted BALB/c nude mice. Crucially, TTCBTA NPs present a strong tumor ablation ability and image-guided PDT effect by generating abundant ROSs upon laser irradiation. These results demonstrate that the TTCBTA NP theranostic nanoplatform may enable highly efficient near-infrared fluorescence image-guided PDT.     

An Intelligent Nanotheranostic Agent for Targeting,Redox‐Responsive Ultrasound Imaging,and Imaging‐Guided High‐Intensity Focused Ultrasound Synergistic Therapy

A novel multifunctional nanotheranostic agent with targeting, redox‐responsive ultrasound imaging and ultrasound imaging‐guided high‐intensity focused ultrasound (HIFU) therapy (MSNC‐PEG‐HA_SS‐PFH, abbreviated as MPH_SS‐PFH) capabilities is developed. The redox‐responsive guest molecule release and ultrasound imaging functions can be both integrated in such a “smart” theranostic agent, which is accomplished by the redox‐triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol‐disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor‐bearing nude mice can be thoroughly and spatial‐accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPH_SS‐PFH in the tumors. This novel multifunctional nano‐platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound‐guidance.     

A Functional CT Contrast Agent for In Vivo Imaging of Tumor Hypoxia

Hypoxia, which has been well established as a key feature of the tumor microenvironment, significantly influences tumor behavior and treatment response. Therefore, imaging for tumor hypoxia in vivo is warranted. Although some imaging modalities for detecting tumor hypoxia have been developed, such as magnetic resonance imaging, positron emission tomography, and optical imaging, these technologies still have their own specific limitations. As computed tomography (CT) is one of the most useful imaging tools in terms of availability, efficiency, and convenience, the feasibility of using a hypoxia‐sensitive nanoprobe (Au@BSA‐NHA) for CT imaging of tumor hypoxia is investigated, with emphasis on identifying different levels of hypoxia in two xenografts. The nanoprobe is composed of Au nanoparticles and nitroimidazole moiety which can be electively reduced by nitroreductase under hypoxic condition. In vitro, Au@BSA‐NHA attain the higher cellular uptake under hypoxic condition. Attractively, after in vivo administration, Au@BSA‐NHA can not only monitor the tumor hypoxic environment with CT enhancement but also detect the hypoxic status by the degree of enhancement in two xenograft tumors with different hypoxic levels. The results demonstrate that Au@BSA‐NHA may potentially be used as a sensitive CT imaging agent for detecting tumor hypoxia.     

Water‐Dispersible Candle Soot–Derived Carbon Nano‐Onion Clusters for Imaging‐Guided Photothermal Cancer Therapy

Herein, water‐dispersible carbon nano‐onion clusters (CNOCs) with an average hydrodynamic size of ≈90 nm are prepared by simply sonicating candle soot in a mixture of oxidizing acid. The obtained CNOCs have high photothermal conversion efficiency (57.5%), excellent aqueous dispersibility (stable in water for more than a year without precipitation), and benign biocompatibility. After polyethylenimine (PEI) and poly(ethylene glycol) (PEG) modification, the resultant CNOCs‐PEI‐PEG have a high photothermal conversion efficiency (56.5%), and can realize after‐wash photothermal cancer cell ablation due to their ultrahigh cellular uptake (21.3 pg/cell), which is highly beneficial for the selective ablation of cancer cells via light‐triggered intracellular heat generation. More interestingly, the cellular uptake of CNOCs‐PEI‐PEG is so high that the internalized nanoagents can be directly observed under a microscope without fluorescent labeling. Besides, in vivo experiments reveal that CNOCs‐PEI‐PEG can be used for photothermal/photoacoustic dual‐modal imaging‐guided photothermal therapy after intravenous administration. Furthermore, CNOCs‐PEI‐PEG can be efficiently cleared from the mouse body within a week, ensuring their excellent long‐term biosafety. To the best of the authors' knowledge, the first example of using candle soot as raw material to prepare water‐dispersible onion‐like carbon nanomaterials for cancer theranostics is represented herein.     

用静态破裂剂破裂混凝土的设计与施工

在环境复杂且不能施爆的情况下，用静态破裂剂破裂岩石或混凝土不失为一条捷径。本文从力学角度分析了静态破裂剂的作用原理，如何确定合理的孔距以及采用空心孔的有关技术，介绍了静态破裂剂的应用及其施工注意事项。     

动态供应链谈判代理的设计及实现

面向动态供应链,引入智能代理技术,充分发挥智能多代理系统的自主性,重点就商业谈判体系以及其功能的设计与实现进行了较为深入的研究.根据业务交易的典型阶段,建立了业务谈判的多代理软件体系,给出了相应的谈判词汇表的描述.确立了谈判规则,并以DFA为工具描述谈判过程,进而实现了一个自主谈判过程.     

Theranostic Upconversion Nanobeacons for Tumor mRNA Ratiometric Fluorescence Detection and Imaging‐Monitored Drug Delivery

Remote optical detection and imaging of specific tumor‐related biomarkers and simultaneous activation of therapy according to the expression level of the biomarkers in tumor site with theranostic probes should be an effective modality for treatment of cancers. Herein, an upconversion nanobeacon (UCNPs‐MB/Dox) is proposed as a new theranostic nanoprobe to ratiometrically detect and visualize the thymidine kinase 1 (TK1) mRNA that can simultaneously trigger the Dox release to activate the chemotherapy accordingly. UCNPs‐MB/Dox is constructed with the conjugation of a TK1 mRNA‐specific molecular beacon (MB) bearing a quencher (BHQ‐1) and an alkene handle modified upconversion nanoparticle (UCNP) through click reaction and subsequently loading with a chemotherapy drug (Dox). With this nanobeacon, quantitative ratiometric upconversion detection of the target with high sensitivity and selectivity as well as the target triggered Dox release in vitro is demonstrated. The sensitive and selective ratiometric detection and imaging of TK1 mRNA under the irradiation of near infrared light (980 nm) and the mRNA‐dependent release of Dox for chemotherapy in the tumor MCF‐7 cells and A549 cells are also shown. This work provides a smart and robust platform for gene‐related tumor theranostics.