核壳结构二氧化硅/磁性纳米粒子的制备及应用

核壳结构二氧化硅/磁性纳米粒子作为一种新型功能复合材料在生物医学方面有重要应用前景.综述了核壳结构二氧化硅/磁性纳米粒子的各种制备方法以及国内外在核壳结构二氧化硅/磁性纳米粒子制备方面的研究新进展,并对其在生物医学上的应用作了介绍.     

Synthesis of silica/Au core-shell nanostructures by galvanic replacement of silica/Ag in aqueous and alkaline medium

We present here a facile one-step method for the synthesis of silica/Au core-shell nanostructures by exploiting the potential difference of AuCl₄^? and Ag in aqueous as well as alkaline media. Initially, silica/Ag core-shell nanostructures were synthesised by coating Ag nanoparticles on silica core (size ～150 nm) in a two-step process (seeding and growth) and were characterised for their morphological, structural and optical behaviours. A complete coverage of silica core with Ag nanoparticles was seen from scanning electron microscope and transmission electron microscope images. The presence of resonance peaks in the optical spectrum manifests the nature of the shell (thin shell ～413 and 650 nm, thick shell ～434 nm). Galvanic replacement of silica/Ag core-shell nanostructures in chloroauric acid solution (HAuCl₄) was studied in both the aqueous and alkaline medium, where an aqueous environment results into fast and effective replacement as compared to an alkaline medium, which has been confirmed from optical absorption studies. The optical studies showed that in an alkaline environment, on galvanic replacement of Ag with Au, the individual absorption peak of Ag (～414 nm) and Au (～520 nm) disappeared, whereas new absorption wavelengths in higher region (600–800 nm) of electromagnetic spectrum were observed. A detailed mechanism is proposed for the same to explain this behaviour. A range of novel new plasmonic core-shell nanomaterials can be synthesised as an intermediate of this facile one-step reaction.     

Effect of Shell Coating Techniques on Dynamic Response of Photoconductive Core/Shell Nanorod Arrays

Efficient carrier collection in the core/shell nanowire (nanorod) arrays requires a high quality interface between core and shell materials. A highly conformal shell layer around nanorods can lead to fast dynamic response in photoconductive devices by a radial charge flow. Therefore, choice of the deposition technique for the conformal shell layer becomes crucial. In this study, the dynamic response of indium sulfide (In₂S₃) nanorods/silver (Ag) core/shell devices is compared in which Ag shell layers are deposited by different physical vapor deposition (PVD) techniques. In₂S₃ nanorods are fabricated by glancing angle deposition. The core/shell devices with Ag shell sputtered at a relatively high working gas pressure (≈3 × 10⁻² mbar) produce the highest photocurrent compared to other devices in which more directional incident flux (with working gas pressure of ≈3 × 10⁻³ mbar) is utilized for Ag shell layer. The reduced transit times indicate a conformal shell achieved by the high pressure sputtering technique that has a wide angular distribution flux. In addition, a more directional flux yet with a small angle (≈30°) incidence with respect to the substrate surface normal also helps increase the photocurrent. Such simple and scalable PVD techniques are shown to offer alternative fabrication approaches in producing high quality core/shell nanostructures.     

叠层开口厚柱壳静、动态分析的变分解

在文献[1－3]的基础上,根据应力变分和伽辽金变分原理导出混合变分方程,并将其转换成状态方程,使状态空间理论和变分原理相结合,给出了正交异性叠层开口柱壳静、动态分析的变分解。此解满足叠层壳的层间连续条件。算例表明,本文的方法具有较高的精度,并能较准确地计算层间应力。     

Screening Therapeutic Agents Specific to Breast Cancer Stem Cells Using a Microfluidic Single‐Cell Clone‐Forming Inhibition Assay

Screens of cancer stem cells (CSCs)‐specific agents present significant challenges to conventional cell assays due to the difficulty in preparing CSCs ready for drug testing. To overcome this limitation, developed is a microfluidic single‐cell assay for screening breast cancer stem cell–specific agents. This assay takes advantage of the single‐cell clone‐forming capability of CSCs, which can be specifically inhibited by CSC‐targeting agents. The single‐cell assay is performed on a microfluidic chip with an array of 3840 cell‐capturing units; the single‐cell arrays are easily formed by flowing a cell suspension into the microchip. Achieved is a single cell‐capture rate of ≈60% thus allowing more than 2000 single cells to be analyzed in a single test. Over long‐term suspension culture, only a minority of cells survive and form tumorspheres. The clone‐formation rate of MCF‐7, MDA‐MB‐231, and T47D cells is 1.67%, 5.78%, and 5.24%, respectively. The clone‐forming inhibition assay is conducted by exposing the single‐cell arrays to a set of anticancer agents. The CSC‐targeting agents show complete inhibition of single‐cell clone formation while the nontargeting ones show incomplete inhibition effects. The resulting microfluidic single‐cell assay with the potential to screen CSC‐specific agents with high efficiency provides new tools for individualized tumor therapy.     

In Vivo Environment‐Adaptive Nanocomplex with Tumor Cell–Specific Cytotoxicity Enhances T Cells Infiltration and Improves Cancer Therapy

Drug delivery strategies possessing selectivity for cancer cells are eagerly needed in therapy of metastatic breast cancer. In this study, the chemotherapeutic agent, docetaxel (DTX), is conjugated onto heparan sulfate (HS). Aspirin (ASP), which has the activity of anti‐metastasis and enhancing T cells infiltration in tumors, is encapsulated into the HS‐DTX micelle. Then the cationic polyethyleneimine (PEI)‐polyethylene glycol (PEG) copolymer binds to HS via electrostatic force, forming the ASP‐loaded HS‐DTX micelle (AHD)/PEI‐PEG nanocomplex (PAHD). PAHD displays long circulation behavior in blood due to the PEG shell. Under the tumor microenvironment with weakly acidic pH, PEI‐PEG separates from AHD, and the free cationic PEI‐PEG facilitates the cellular uptake of AHD by increasing permeability of cell membranes. Then the overexpressed heparanase degrades HS, releasing ASP and DTX. PAHD shows specific toxicity toward tumor cells but not normal cells, with advanced activity of inhibiting tumor growth and lung metastasis in 4T1 tumor‐bearing mice. The number of CD8⁺ T cells in tumor tissues is also increased. Therefore, PAHD can become an efficient drug delivery system for breast cancer treatment.     

斜拉桥动力性能分析

对一座塔墩固结、主梁连续半飘浮体系的斜拉桥，分别采用两种不同的单元类型进行动力性能的对比研究，并将结果与上海南浦大桥的动力特性进行对比，从而得出研究斜拉桥动力特性时应选择能准确反映实际构件性质的单元类型，且最好建立全桥模型来模拟实际桥梁结构的结论。     

水热还原法制备Ag@C壳核纳米结构及其表征

以棉花纤维制备的纤维素微晶为碳源,采用水热还原法制备了Ag@C壳核结构纳米颗粒,并用扫描电子显微镜、投射电子显微镜、X射线能谱仪、X射线衍射仪对产品进行表征,结果表明,所得产品为Ag@C核／壳结构纳米颗粒,外壳是碳层,内核为纳米银颗粒。最佳的制备条件是,180％反应15h,pH=1-2,纤维素微晶的浓度为0．083g／L。讨论了碳包银核／壳结构的生长机理,     

Fabrication and Mechanical Properties of Large‐Scale Freestanding Nanoparticle Membranes

Thin‐film membranes consisting of nanoparticles are of interest in applications ranging from nanosieves to electric, magnetic, or photonic devices and sensors. However, the fabrication of large‐scale membranes in a simple but controlled way has remained a challenge, due to the limited understanding of their mechanical properties. Systematic experiments on ultrathin, freestanding nanoparticle membranes of different core materials, core sizes, and capping ligands are reported. The results demonstrate that a drying‐mediated self‐assembly process can be used to create close‐packed monolayer membranes that span holes tens of micrometers in diameter. Containing up to ≈10⁷ particles, these freely suspended layers exhibit remarkable mechanical properties with Young's moduli of the order of several GPa, independent of membrane size. Comparison of three different core–ligand combinations suggests that the membrane's elastic response is set by how tightly the ligands are bound to the particle cores and by the ligand–ligand interactions.     

圆锥薄壳体瞬态动力响应分析

运用有限元分析软件ANSYS／LS-DYNA对在余弦脉冲载荷作用下某圆锥薄壳体的瞬态动力响应过程进行分析，得出了不同时刻下壳体等效应力场的分布，考察了该壳体结构的动强度性能。同时通过对一些典型节点位移、速度和应力响应曲线的分析，归纳总结出了在余弦脉冲加载条件下圆锥薄壳体瞬态响应的规律，对该壳体的结构设计和改型提出了合理化建议，并定性地分析了该脉冲加载对壳体内部电子设备的影响。最后，将理论计算和试验结果进行对比分析，验证了计算模型的正确性。     

Biophysical Phenotyping and Modulation of ALDH+ Inflammatory Breast Cancer Stem‐Like Cells

Cancer stem‐like cells (CSCs) have been shown to initiate tumorigenesis and cancer metastasis in many cancer types. Although identification of CSCs through specific marker expression helps define the CSC compartment, it does not directly provide information on how or why this cancer cell subpopulation is more metastatic or tumorigenic. In this study, the functional and biophysical characteristics of aggressive and lethal inflammatory breast cancer (IBC) CSCs at the single‐cell level are comprehensively profiled using multiple microengineered tools. Distinct functional (cell migration, growth, adhesion, invasion and self‐renewal) and biophysical (cell deformability, adhesion strength and contractility) properties of ALDH+ SUM149 IBC CSCs are found as compared to their ALDH? non‐CSC counterpart, providing biophysical insights into why CSCs has an enhanced propensity to metastasize. It is further shown that the cellular biophysical phenotype can predict and determine IBC cells' tumorigenic ability. SUM149 and SUM159 IBC cells selected and modulated through biophysical attributes—adhesion and stiffness—show characteristics of CSCs in vitro and enhance tumorigenicity in in vivo murine models of primary tumor growth. Overall, the multiparametric cellular biophysical phenotyping and modulation of IBC CSCs yields a new understanding of IBC's metastatic properties and how they might develop and be targeted for therapeutic interventions.     

Detection of Circulating Cancer Cells Using Electrocatalytic Gold Nanoparticles

A rapid cancer cell detection and quantification assay, based on the electrocatalytic properties of gold nanoparticles towards the hydrogen evolution reaction, is described. The selective labeling of cancer cells is performed in suspension, allowing a fast interaction between the gold nanoparticle labels and the target proteins expressed at the cell membrane. The subsequent electrochemical detection is accomplished with small volumes of sample and user‐friendly equipment through a simple electrochemical method that generates a fast electrochemical response used for the quantification of nanoparticle‐labeled cancer cells. The system establishes a selective cell‐detection assay capable of detecting 4 × 10³ cancer cells in suspension that can be extended to several other cells detection scenarios.     

拉索_网壳结构的动力特性和非线性动力反应

将空间网壳结构与拉索有机结合便形成拉索-网壳结构体系。该体系不但具有美学特征，更可进一步增大跨度。基于泰勒数学展开公式和变分原理，推导了具有二阶精度的空间杆单元几何非线性刚度矩阵；研究了拉索单元非线性问题，得出了其切线刚度矩阵；给出了结构非线性力学响应计算策略等。通过数值计算，分析了结构动力特性和非线性地震动力响应问题。计算结果显示，拉索-网壳结构的自振频率皆明显高于对应的网壳结构，且频谱较为密集，甚至不同序号的自振频率几乎相同，拉索-网壳结构的地震动力响应不但与拉索长度、截面尺寸、预拉力和布置方式有关，还与塔柱高度、截面尺寸等有关。     

Surface‐Engineering of Red Blood Cells as Artificial Antigen Presenting Cells Promising for Cancer Immunotherapy

The development of artificial antigen presenting cells (aAPCs) to mimic the functions of APCs such as dendritic cells (DCs) to stimulate T cells and induce antitumor immune responses has attracted substantial interests in cancer immunotherapy. In this work, a unique red blood cell (RBC)‐based aAPC system is designed by engineering antigen peptide‐loaded major histocompatibility complex‐I and CD28 activation antibody on RBC surface, which are further tethered with interleukin‐2 (IL2) as a proliferation and differentiation signal. Such RBC‐based aAPC‐IL2 (R‐aAPC‐IL2) can not only provide a flexible cell surface with appropriate biophysical parameters, but also mimic the cytokine paracrine delivery. Similar to the functions of matured DCs, the R‐aAPC‐IL2 cells can facilitate the proliferation of antigen‐specific CD8+ T cells and increase the secretion of inflammatory cytokines. As a proof‐of‐concept, we treated splenocytes from C57 mice with R‐aAPC‐IL2 and discovered those splenocytes induced significant cancer‐cell‐specific lysis, implying that the R‐aAPC‐IL2 were able to re‐educate T cells and induce adoptive immune response. This work thus presents a novel RBC‐based aAPC system which can mimic the functions of antigen presenting DCs to activate T cells, promising for applications in adoptive T cell transfer or even in direct activation of circulating T cells for cancer immunotherapy.     

Biomimetic Nanobomb for Synergistic Therapy with Inhibition of Cancer Stem Cells

Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever. In this work, a nanotherapeutic strategy based on MnO_x-loaded polydopamine (MnO_x/PDA) nanobombs with chemodynamic, photodynamic, photothermal and biodegradation properties to inhibit CSCs and non-CSCs concurrently is reported. The MnO_x/PDA nanobombs can directly disrupt the microenvironment and tumorigenic capacity of CSCs by generating hyperthermia, oxidative stress and alleviating hypoxia. The markers of CSCs are subsequently downregulated, leading to the clearance of CSCs. Meanwhile, the synergistic therapy mediated by MnO_x/PDA nanobombs can directly ablate the bulk tumor cells, thus cutting off the supply of CSCs transformation. For tumor targeting, MnO_x/PDA is coated with macrophage membrane. The final tumor inhibition rate of the synergistic therapy is 70.8% in colorectal cancer (CRC) model. Taken together, the present work may open up the exploration of nanomaterial-based synergistic therapy for the simultaneous elimination of therapeutically resistant CSCs and non-CSCs.     

Capturing Cancer: Emerging Microfluidic Technologies for the Capture and Characterization of Circulating Tumor Cells

Circulating tumor cells (CTCs) escape from primary or metastatic lesions and enter into circulation, carrying significant information of cancer progression and metastasis. Capture of CTCs from the bloodstream and the characterization of these cells hold great significance for the detection, characterization, and monitoring of cancer. Despite the urgent need from clinics, it remains a major challenge to capture and retain these rare cells from human blood with high specificity and yield. Recent exciting advances in micro/nanotechnology, microfluidics, and materials science have enable versatile, robust, and efficient cell isolation and processing through the development of new micro/nanoengineered devices and biomaterials. This review provides a summary of recent progress along this direction, with a focus on emerging methods for CTC capture and processing, and their application in cancer research. Furthermore, classical as well as emerging cellular characterization methods are reviewed to reveal the role of CTCs in cancer progression and metastasis, and hypotheses are proposed in regard to the potential emerging research directions most desired in CTC‐related cancer research.