Recent advances in biological-environment-responsive smart MRI contrast agents

随着生物医学领域的不断发展,人们对于在分子机理层面上研究生物体系中新陈代谢、疾病的发生和发展等过程的需求日益增长.磁共振成像因拥有其他成像方法所; 不具备的非侵入式、深层次的空间分辨能力,为生物体系分子层面的检测提供了有力的工具.分子层面的磁共振成像检测离不开生物环境智能响应磁共振造影剂的使; 用.生物环境智能响应磁共振造影剂的造影能力会随着特定生物环境变化而发生改变.此类造影剂使得人们可以根据磁共振图像上信号的改变分析得到生物体特定位; 置的pH、离子浓度、酶活力等相关信息.近20年来,生物环境智能响应磁共振造影剂得到了长足的发展.本文将按不同的响应对象分类总结近几年此类造影剂的; 研究进展,并对一些重要的研究成果进行较为详细的阐述和对比,分析目前生物环境智能响应磁共振造影剂研究中存在的困难和解决方案,最后对本领域的进一步发; 展进行展望.With the rapid advancement in biology and medicine, there is an urgent; need to study metabolisms in lives and mechanisms of diseases at; molecular levels. Magnetic resonance imaging (MRI), which is capable of; non-invasive and three-dimensional deep imaging, is a powerful tool to; meet this demand. Environment-responsive contrast agents, whose contrast; abilities change once stimulated, are necessary for this purpose. With; the use of these responsive contrast agents, related biological; information, such as pH, concentration of ions, activity of enzymes,; could be easily extracted and analyzed from MR images. Considerable; progress has been made in the field of biological-environment-responsive; smart MRI contrast agents over the two decades. In this review, we; describe achievements in recent years, discuss several representative; works in detail, summarize current difficulties that have been met and; possible solutions that have been formulated, and finally look into the; promising future of biological-environment-responsive smart MRI contrast; agents.科技部973项目; 国家自然科学基金; 霍英东教育基

Facile, sensitive, and ratiometric detection of mercuric ions using GSH-capped semiconductor quantum dots

National Key Basic Research Program of China [2013CB933901]; National Natural Science Foundation of China [21222106, 21021061, 81000662, 81201805]; Fundamental Research Funds for the Central Universities [2010121012]; Scientific Research Foundation for the Returned Overseas Chinese Scholars; Program for New Century Excellent Talents in University [NCET-10-0709]Glutathione (GSH) capped CdTe semiconductor quantum dots (QDs) are applied for detecting mercuric ions (Hg2+) of trace quantity. The synthesis of GSH-capped CdTe (CdTe@GSH) QDs is cost-efficient and straightforward. We observed that Hg2+ can quantitatively quench the fluorescence of CdTe@GSH QDs and further induce the slight redshift of emission peaks due to the quantum confinement effect. Detailed studies by spectroscopy, dynamic light scattering (DLS), and electrospray ionization mass spectrometry (ESI-MS) demonstrated that the competitive Hg2+ binding with GSH makes the surface of CdTe QDs exposed, results in gradual aggregation, and quantitatively changes the photophysical properties of QDs. The whole procedure for detecting Hg2+ by this protocol took less than 10 min. The experimental limit of detection (LOD) of Hg2+ can be as low as 5 nM using CdTe@GSH with a low concentration (0.5 nM) because of the excellent fluorescent properties of QDs. This strategy may become a promising means to simply detect Hg2+ in water with high sensitivity

FePt@CoS2 yolk-shell nanocrystals as a potent agent to kill HeLa cells

In situ gap-mode Raman spectra were acquired in an electrochemical environment on a single-crystal gold electrode employing a Au(100)|4,4'-biphenyldithiol (BPDT)|Au-NP(55 nm) sandwich assembly. This geometry enabled an investigation of the influence of an applied electrochemical gate field on the conformational changes in nanojunctions, such as the torsion angle (phi) of molecules. A linear correlation between the intensity ratio I-C=C/ICring-S and cos(2) phi in 4,4'-BPDT-type molecular junctions was established and subsequently utilized to estimate the potential dependence of the torsion angle of the "flexible" molecule M1 at different potentials. The latter decreases as the potential (charge) becomes more negative, resulting in better pi-pi coupling, which correlates with enhanced junction conductance. The demonstrated spectroelectrochemical strategy and the direct correlation of the spectroscopic results with (single) molecular conductance studies may guide the selection and elucidation of functional molecules for potential applications in novel nanodevices

A fluorescent switch for sequentially and selectively sensing copper(II) and L-histidine in vitro and in living cells

National Natural Science Foundation of China [21175122, 91127036, 21375121]; Fundamental Research Funds for Central Universities [WK2060190018]Herein, we report the development of a new fluorescent switch for sequential and selective sensing of Cu2+ and L-histidine (L-His) in vitro and in living cells for the first time. In the absence of metal ions, Ac-SAACQ- Gly-Gly-Gly-Lys (FITC) (1) exhibits comparable fluorescence to that of free FITC. In the presence of metal ions, 1 selectively coordinates to Cu2+, causing its fluorescence emission to be quenched via photoinduced electron transfer. Interestingly, the as-formed 1-Cu2+ complex selectively responds to L-His among the 20 natural amino acids by turning its fluorescence on. This property of fluorescence switch of 1 was successfully applied for qualitatively and quantitatively sensing Cu2+ and L-His in vitro. Using this dual functional probe, we also sequentially imaged Cu2+ and L-His in living HepG2 cells. Our new probe 1 could be applied for not only environmental monitoring but also biomolecule detection in the near future

Understanding the metabolic fate and assessing the biosafety of MnO nanoparticles by metabonomic analysis

National Natural Science Foundation of China [20605025, 81272581]; Fundamental Research Funds for the Central Universities [2011121046]Recently, some types of MnO nanoparticle (Mn-NP) with favorable imaging capacity have been developed to improve the biocompatible profile of the existing Mn-based MRI contrast agent Mn-DPDP; however, the overall bio-effects and potential toxicity remain largely unknown. In this study, H-1 NMR-based metabolic profiling, integrated with traditional biochemical analysis and histopathological examinations, was used to investigate the absorption, distribution, metabolism, excretion and toxicity of Mn-NPs as candidates for MRI contrast agent. The metabolic responses in biofluids (plasma and urine) and tissues (liver, spleen, kidney, lung and brain) from rats could be divided into four classes following Mn-NP administration: Mn biodistribution-dependent, time-dependent, dose-dependent and complicated metabolic variations. The variations of these metabolites involved in lipid, energy, amino acid and other nutrient metabolism, which disclosed the metabolic fate and biological effects of Mn-NPs in rats. The changes of metabolic profile implied that the disturbance and impairment of biological functions induced by Mn-NP exposure were correlated with the particle size and the surface chemistry of nanoparticles. Integration of metabonomic technology with traditional methods provides a promising tool to understand the toxicological behavior of biomedical nanomaterials and will result in informed decision-making during drug development

Multifunctional Ag@Fe(2)O(3) yolk-shell nanoparticles for simultaneous capture, kill, and removal of pathogen

We combined silver and iron oxide nanoparticles to make unique Ag@Fe(2)O(3) yolk-shell multifunctional nanoparticles by the Kirkendall effect. After the surface functionalization using glucose, the Ag@Fe(2)O(3)-Glu conjugates exhibited both high capture efficiency of bacteria and potent antibacterial activity. The Ag@Fe(2)O(3) yolk-shell nanostructures may offer a unique multifunctional platform for simultaneous rapid detection and capture of bacteria and safe detoxification treatment.National Science Foundation of China[21021061, 81000662]; Fundamental Research Funds for the Central Universities[2010121012]; Program for New Century Excellent Talents in University[NCET-10-0709

PET/NIRF/MRI triple functional iron oxide nanoparticles

Engineered nanoparticles with theranostic functions have attracted a lot of attention for their potential role in the dawning era of personalized medicine. Iron oxide nanoparticles (IONPs), with their advantages of being non-toxic, biodegradable and inexpensive, are candidate platforms for the buildup of theranostic nanostructures; however, progress in using them has been limited largely due to inefficient drug loading and delivery. In the current study, we utilized dopamine to modify the surface of IONPs, yielding nanoconjugates that can be easily encapsulated into human serum albumin (HSA) matrices (clinically utilized drug carriers). This nanosystem is well-suited for dual encapsulation of IONPs and drug molecules, because the encapsulation is achieved in a way that is similar to common drug loading. To assess the biophysical characteristics of this novel nanosystem, the HSA coated IONPs (HSA-IONPs) were dually labeled with (64)Cu-DOTA and Cy5.5, and tested in a subcutaneous U87MG xenograft mouse model. In vivo positron emission tomography (PET)/near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) tri-modality imaging, and ex vivo analyses and histological examinations were carefully conducted to investigate the in vivo behavior of the nanostructures. With the compact HSA coating, the HSA-IONPs manifested a prolonged circulation half-life; more impressively, they showed massive accumulation in lesions, high extravasation rate, and low uptake of the particles by macrophages at the tumor area. Published by Elsevier Ltd

Highly magnetic iron carbide nanoparticles as effective T2 contrast agents

This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (～20 nm in diameter) exhibit strong contrast enhancement with an r2 value of 283.2 mM-1 S-1, which is about twice as high as that of spherical Fe3O4 nanoparticles (～140.9 mM-1 S-1). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O 4 nanoparticles in living subjects, which holds great promise in biomedical applications. ? 2013 The Royal Society of Chemistry

Highly magnetic iron carbide nanoparticles as effective T-2 contrast agents

National Key Basic Research Program of China [2013CB933901, 2014CB744502]; National Natural Science Foundation of China [21222106, 81370042, 81000662, 81201805]; Natural Science Foundation of Fujian [2013J06005]; Program for New Century Excellent Talents in University [NCET-10-0709]This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T-2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (similar to 20 nm in diameter) exhibit strong contrast enhancement with an r(2) value of 283.2 mM(-1) S-1, which is about twice as high as that of spherical Fe3O4 nanoparticles (similar to 140.9 mM(-1) S-1). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O4 nanoparticles in living subjects, which holds great promise in biomedical applications

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

磁性探针作为分子影像技术中的磁共振成像（MRI）造影剂在医学诊断中发挥着重要作用。为满足实际诊断中的准确性和精确性要求，科研工作者们长期致力于发展高性能的MRI造影剂以降低高剂量的使用带来的潜在风险。该文章指出了探针聚集体中局域磁场不均匀性是影响T2弛豫效能的关键因素。该文章首次利用磁场不均匀性因素阐明了单个探针和它们聚集体的MRI造影剂之间的相互关系，将可能成为弥补探针聚集体的造影剂理论的空白，并为发展新型高效的MRI造影剂提供重要参考。 该论文共同第一作者为博士后周子健和博士生田蕊，通讯作者为陈小元教授和聂立铭博士，部分工作得到我校物理学系王瑞方教授和化学化工学院高锦豪教授的支持。【Abstract】Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents.This work was supported by the National Science Foundation of China (81571744 and 81601489), the National Basic Research Program of China (863 Program 2015AA020502), the Fundamental Research Funds for the Central Universities (20720170065), the Science Foundation of Fujian Province (No. 2014Y2004), and by the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). 研究工作得到了国家自然科学基金委、国家高技术研究发展计划863项目、福建省重大研发平台项目和美国NIH Intramural Research Program的资助