Functionalized Magnetite Nanoparticles—Synthesis,Properties, and Bio-Applications

Nanotechnology has generated tremendous hopes in recent years toward the design of advanced functional materials, especially in the bio-medical field. Nano-sized-materials such as magnetite nanoparticles display indeed fascinating physico-chemical properties that, if tuned properly, can be exploited to design new bio-diagnostic and therapeutic strategies as well as innovative biotechnology methodologies. Owing to their biocompatibility and excellent magnetic properties, magnetite nanocrystals have been the object of a tremendous amount of research in the last decade and numerous (bio)applications have been reported. Importantly, advances in the synthesis of magnetite nanoparticles enable excellent control over their size, shape, and composition. Despite these remarkable progresses, many issues remain to be overcome for these nanotechnology products to revolution the medical practice. The fine control and application of colloidal nanostructures such as magnetite nanoparticles in complex biological systems remains especially challenging. This article attempts to review the current status of magnetite nanoparticles preparation and use, with a special emphasis on bio-medical applications, but also to outline the promises and challenges associated to this emerging technology.     

Correlation of Electronic and Magnetic Properties of Thin Polymer Layers with Cobalt Nanoparticles

Nanoparticles (NPs) of cobalt are synthesized in shallow layers of polyimide using 40 keV implantation of Co⁺ ions with a few different fluences at various ion current densities. Nucleation of individual NPs at low fluencies and their percolation at high fluencies are crucial processes governing the electrical and magnetic properties of the metal/polymer nanocomposites that can be controlled by the implantation regimes. In particular, one can tune the magnetoresistance between negative and positive through appropriate choice of ion fluence and current density. The found non‐monotonous dependence of the magnetoresistance on the applied magnetic field allows suggestion of spin‐dependent domain wall scattering affecting the electron transport. The samples implanted with low fluencies demonstrate superparamagnetic behavior down to very low blocking temperatures. For high fluence (1.25 × 10¹⁷ cm⁻²) the transition to ferromagnetic ordering is observed that is related to the increased magnetic interaction of NPs.     

NIR‐Triggered Release of Nitric Oxide with Upconversion Nanoparticles Inhibits Platelet Aggregation in Blood Samples

There is a great challenge to overcome the limitation of tissue penetration depth, while maximizing the benefit of light‐triggered biochemical cascades in a well‐defined mode simultaneously. Here, a new method of near‐infrared (NIR) light‐triggered release of nitric oxide (NO) by developing upconversion nanoparticles (UCNPs)‐based conjugate chemistry is reported. As the key nanotransducer in the design, core–shell‐structured UCNPs are encapsulated with a layer of SiO₂ and then covalently linked with a potent NO‐releasing donor (S‐nitroso‐N‐acetyl‐dl ‐penicillamine, SNAP). It is featured with highly localized breakage of chemical bonds of SNAP molecules by NIR–UV upconversion, enabling simultaneous NO release in a light dosage‐dependent manner. The biological effects of NO releasing are demonstrated by cellular imaging and inhibition of platelet aggregation from blood samples. This work provides a flexible and robust platform to generate cell‐signaling gas molecules trigged by NIR laser with deep tissue penetration.     

Determination of Conjugation Efficiency of Antibodies and Proteins to the Superparamagnetic Iron Oxide Nanoparticles by Capillary Electrophoresis with Laser-Induced Fluorescence Detection

The method based on capillary electrophoresis with laser-induced fluorescence detection (CE/LIF) was developed for determination of magnetic iron oxide nanoparticles (hydrodynamic diameters of 100 nm) functionalized with molecules containing primary amino groups. The magnetic nanoparticles with carboxylic or aminopropyl-trimethoxysilane groups at their surface were conjugated to the model proteins (bovine serum albumin, BSA; streptavidin or goat anti-rabbit immunoglobulin G, IgG) using carbodiimide as a zero-length cross-linker.The nanoparticle–protein conjugates (hydrodynamic diameter 163–194 nm) were derivatized with naphthalene-2,3-dicarboxaldehyde reagent and separated by CE/LIF with a helium–cadmium laser (excitation at 442 nm, emission at 488 nm). The separations were carried out by using a fused-silica capillary (effective length 48 cm, inner diameter 75 um) and 100 mM sodium borate buffer (pH 9.2), the potential was 30 kV. The detection limit for BSA-conjugate was 1.3 pg/10 nl, i.e. about 20 amol. The present method provides an efficient and fast tool for sensitive determination of the efficacy of biomolecular functionalization of magnetic nanoparticles. The CE/LIF technique requires only negligible sample volumes for analysis, which is especially suitable for controlling the process of preparation of functionalized nanoparticles with unique properties aimed to be used for diagnostic or therapeutic purposes.     

Controlled Release of an Antihypertensive Drug through Interpenetrating Polymer Network Hydrogel Tablets of Tamarind Seed Polysaccharide and Sodium Alginate

The application of interpenetrating polymer network (IPN) hydrogel tablets of tamarind seed polysaccharide and sodium alginate for controlled release of a water-soluble antihypertensive drug, propranolol HCl (PPL), was investigated. The IPN tablets loaded with PPL or PPL–resin complex (resinate) were prepared by a wet granulation/covalent cross-linking method. Fourier Transform Infrared Spectroscopic confirmed the cross-linking reaction and IPN formation, while X-ray Diffraction and Scanning Electron Microscopy studies confirmed the amorphous dispersion of the drug within the IPN tablets. The plain drug PPL showed complete release within 1 h, while drug release from the resinate was prolonged for 2.5 h and the IPN matrices showed drug release up to 24 h. The drug release rate from the IPN matrices was affected by polymer concentration and cross-linking time; the higher the cross-linking time, the slower was the drug release. The drug release mechanism was found to be of a non-Fickian type.     

Uptake and Intracellular Fate of Peptide Surface‐Functionalized Silica Hybrid Magnetic Nanoparticles In Vitro

Recently, the use of nanomaterials as intracellular targeting tools for theranostics has gained heightened interest. Despite the clear advantages posed by surface‐functionalized nanoparticles (NPs) in this regard, limited understanding currently exists due to difficulties in reliably synthesizing NPs with surface functionalizations adequate for use in such applications, as well as the manner of analytics used to assess the cellular uptake and intracellular localization of these NPs. In the present study, two key surface functionalities (a nuclear localization sequence (NLS) and integrin‐ligand (cRGD)) are attached to the surface of multifunctional, silica hybrid magnetic nanoparticles (SHMNPs) containing a polyethylene glycol (PEG) polymer coating using a well‐described, reliable, and reproducible microreactor set‐up. Subsequent analytical interpretation, via laser scanning confocal, transmission electron and dark‐field microscopy, as well as flow cytometry, of the interaction of SHMNPs‐PEG‐cRGD‐NLS with macrophage (J774A.1) and epithelial (HeLa) cells shows internalization of the SHMNPs‐PEG‐cRGD‐NLS in both cell types up to 24 h after 20 μg mL^?1 exposure, as well as increasing aggregation inside of vesicles over this time period. The findings of this study show that by incorporating a variety of state‐of‐the‐art analytical and imaging approaches, it is possible to determine the specific effectiveness of surface peptide and ligand sequences upon multifunctional SHMNPs.     

Facile Synthesis of Lactobionic Acid‐Targeted Iron Oxide Nanoparticles with Ultrahigh Relaxivity for Targeted MR Imaging of an Orthotopic Model of Human Hepatocellular Carcinoma

Development of multifunctional nanoprobes for tumor diagnosis is extremely important in the field of molecular imaging. In this study, the facile synthesis of lactobionic acid (LA)‐targeted superparamagnetic iron oxide (Fe₃O₄) nanoparticles (NPs) with ultrahigh relaxivity for targeted magnetic resonance (MR) imaging of an orthotopic hepatocellular carcinoma (HCC) is reported. Polyethyleneimine (PEI)‐stabilized Fe₃O₄ NPs prepared via a mild reduction route are sequentially coupled with fluorescein isothiocyanate and polyethylene glycol‐LA (LA‐PEG‐COOH) segment, followed by acetylation of the remaining PEI surface amines. The formed LA‐targeted Fe₃O₄ NPs are thoroughly characterized. It is shown that the developed multifunctional LA‐targeted Fe₃O₄ NPs are colloidally stable and water‐dispersible, display an ultrahigh r ₂ relaxivity (579.89 × 10^?3 m ^?1 s^?1) and excellent hemocompatibility and cytocompatibility in the given concentration range, and can target HepG2 cells overexpressing asialoglycoprotein receptors as confirmed by in vitro cellular uptake assay, flow cytometry, and confocal microscopy. Most strikingly, the developed multifunctional LA‐targeted Fe₃O₄ NPs can be used as a nanoprobe for targeted MR imaging of HepG2 cells in vitro and an orthotopic tumor model of HCC in vivo. With the ultrahigh r ₂ relaxivity and the versatile PEI amine‐mediated conjugation chemistry, a range of different Fe₃O₄ NP‐based nanoprobes may be developed for theranostics of different types of cancer.     

氧化物纳米材料表面结构与性质的固体核磁共振波谱研究

氧化物纳米材料的多种应用与其表面结构和性质密切相关.近年来,固体核磁共振波谱在相关研究中提供了关键信息.本综述总结了近期发展的、以固体核磁共振波谱为主的两种表征氧化物纳米材料表面结构和性质的方法,包括表面选择的同位素标记¹⁷O核磁共振波谱与动态核极化表面增强核磁共振波谱,并对氧化物纳米材料的固体核磁共振波谱研究的发展趋势进行了展望.     

Construction of a Dual Drug Carrier on the Basis of Hollow Structured Upconversion Nanoparticles for pH‐Responsive Drug Delivery and UCL/MRI Dual Mode Imaging

A series of Gd³⁺ doping hollow upconversion nanoparticles NaYF₄:Yb,Gd,Tm (h‐UNCP) are prepared successfully. The hollow NaYF₄:Yb,Gd,Tm possess excellent upconversion luminescence (UCL) and large longitudinal relativity (r₁ = 128.3 mm ^?1 s^?1), which can be potentially used for UCL/magnetic resonance imaging (MRI) dual mode imaging. On the basis of the optimal h‐UCNP, doxorubicin hydrochloride (DOX) and methotrexate (MTX) are used as drug models to prepare a dual drug carrier. After the encapsulation of DOX on the h‐UCNP, chitosan (CS) is further wrapped and then used to load MTX to obtain a dual drug carrier h‐UCNPs/DOX/CS/MTX. The pH responsive release of DOX and MTX is discussed. The MTX release climbs from 33% to 100% by regulating the pH from 5.8 to 7.4. The DOX release is different at different pH conditions. The synergistic effect of DOX and MTX on the cancer cells is confirmed by cell viability. The h‐UCNPs/DOX/CS/MTX are tracked by cells UCL imaging and vivo MRI imaging. The excellent performance of UCL imaging and positive MRI images demonstrates that h‐UCNPs/DOX/CS/MTX can be used for UCL/MRI dual mode imaging. All the results show the potential application of h‐UCNPs/DOX/CS/MTX in pH responsive release and UCL/MRI dual imaging.     

兼具磁共振响应的碳量子点光致发光材料的构筑和性能

碳量子点作为光功能组分和纳米载体用于构筑磁共振-荧光双模态分子探针的研究才刚刚开始。本文首次以兼作Gd3+源和碳源的钆喷酸单葡甲胺为前驱体,研究了热裂解温度、保温时间和加热速率对前驱体碳化程度、所得产物量子产率和Gd3+掺杂量的影响。结果显示,前驱体在经历合理的热裂解条件(热裂解温度不高于350℃)后,可简便地制得Gd3+螯合物掺杂的碳量子点。该碳量子点除了具有优异的发光能力外(量子产率~7.6%),还表现出磁共振响应(纵向弛豫率~6.5 mmol-1·L·s-1),可用作磁共振-荧光双模态分子影像探针。     

基于多模态MRI与深度学习的乳腺病变良恶性鉴别

为提高基于动态增强磁共振成像（DCE-MRI）的计算机辅助（CAD）方法对乳腺病变良恶性鉴别的精度,本文基于多模态特征融合,提出一种联合非对称卷积和超轻子空间注意模块的卷积神经网络AC_Ulsam_CNN.首先,采用迁移学习方法预训练模型,筛选出对乳腺病变良恶性鉴别最为有效的DCE-MRI扫描时序.而后,基于最优扫描时序图像,搭建基于AC_Ulsam_CNN网络的模型,以增强分类模型的特征表达能力和鲁棒性.最后,将影像特征与乳腺影像数据报告和数据系统（BI-RADS）分级、表观扩散系数（ADC）和时间-信号强度曲线（TIC）类型等多模态信息进行特征融合,以进一步提高模型对病灶的预测性能.采用五折交叉验证方法进行模型验证,本文方法获得了0.826的准确率（ACC）和0.877的受试者工作曲线下面积（AUC）.这表明该算法在小样本量数据下可较好区分乳腺病变的良恶性,而基于多模态数据的融合模型也进一步丰富了特征信息,从而提高病灶的检出精度,为乳腺病灶良恶性的自动鉴别诊断提供了新方法.     

包覆镍铁氧体纳米粒子的空心玻璃微珠复合材料的制备与电磁性能研究

"用高分子凝胶法制备了包覆镍铁氧体纳米粒子的空心玻璃微珠复合材料．玻璃微珠含量为25%、50%和75%的复合粉的结构、表面形貌和电磁性能分别用X射线衍射仪、扫描电镜、能谱仪、红外光谱和HP8510网络分析仪来表征．结果表明,复合粉由镍铁氧体、石英和莫来石相组成．随着微珠含量的增加,镍铁氧体衍射峰强度迅速降低,莫来石衍射峰强度迅速增强．当温度达到800 ℃时,纯尖晶石结构的镍铁氧体在玻璃微珠表面生成．当玻璃微珠含量为50%时可获得均一、连续的镍铁氧体涂层．大部分镍铁氧体粒子的尺寸小于80 nm．玻璃微珠含量     

A study of the use of Overhauser enhancement to assist with needle and catheter placement during interventional MRI

The practicability of using Overhauser enhancement of saline in interventional MRI was investigated. Saline was used as a means of marking the path taken by a fluid-filled cavity, similar to that formed by a needle, catheter, or cannula during interventional MRI procedures. A prototype device was designed and constructed for saturation and propulsion of 0.6 ml of doped liquid. The pertinent Overhauser parameters, such as the obtainable enhancement factor, were measured. Signal enhancement in excess of 10 was demonstrated in practice by acquiring images showing an enhancement of fluid in a catheter tube.