pH-responsive metal nanoparticles as high contrast theranostic agents for selective imaging and synergistic cancer therapy

The low signal-to-noise ratio(S/N)and single functionality of fluorescence imaging agents have limited their practical applications.Bright two-photon excitation(2PE)imaging probes are highly desirable in vivo with larger imaging depth,minor autofluorescence background,and less photodamage.Herein,we developed responsive aggregated gold nanoparticles(Au NPs)as high contrast 2PE imaging agents,capable of emitting red fluorescence upon excitation of near-infrared(NIR)laser and possessing a high signal-to-noise ratio(S/N of 2,475).By forming aggregates in situ inside tumor tissue,doxorubicin hydrochloride(DOX)-loaded mix-charged gold nanoparticles(DOX-MC-Au NPs)were utilized to act as selective fluorescence imaging probes and precise therapy agents.These high-contrast theranostic agents offer a promising potential for precise cancer imaging and therapy,which might open a new venue to multifunctional and noninvasive theranostics.

Gadolinium-hyaluronic acid nanoparticles as an efficient and safe magnetic resonance imaging contrast agent for articular cartilage injury detection

Accurate detection of cartilage injuries is critical for their proper treatment because these injuries lack the selfhealing ability and lead to joint dysfunction.However,the low longitudinal T1 relaxivity(r1)and non-specificity of contrast agents(such as gadolinium(III)-diethylenetriamine-pentaacetic acid(Gd-DTPA))significantly limit the efficiency of clinical magnetic resonance imaging(MRI)applications.To overcome these drawbacks,we integrated hyaluronic acid(HA)with Gd to synthesize a Gd-DTPA-HA composite,which was subsequently freeze-dried to produce nanoparticles(NPs).The resultant Gd-HA NPs demonstrated a greater r1 value(12.51 mM^-1 s^-1)compared with the bulk Gd-DTPA-HA(8.37 mM^-1 s^-1)and clinically used Gd-DTPA(3.88 mM^-1 s^-1).Moreover,the high affinity of HA to the cartilage allowed these NPs to penetrate deeper beyond the cartilage surface.As a result,Gd-HA NPs considerably increased the quality of cartilage and lesion MR images via their intra-articular injection in vivo.Specifically,2 h after NP administration,the signal-to-noise ratio at the injured cartilage site was 2.3 times greater than the value measured before the injection.In addition,Gd-HA NPs exhibited good biosafety properties due to the absence of adverse effects in the blood or on the main organs.It was also showed that Gd NPs were first metabolized by the kidney and liver and then excreted from the body with urine.Thus,Gd-HA NPs can potentially serve as an efficient MRI contrast agent for improved detection of cartilage injuries.

Myocardial perfusion imaging with a contrast agent at a low concentration in the diagnosis of myocardial infarction in the elderly

Objective To evaluate the clinical value of myocardial perfusion imaging with dual-source dual-energy CT and a contrast agent at a low concentration in the diagnosis of myocardial infarction in the elderly.Methods Onestop cardiac imaging with dual-source CT was conducted in 138 elderly patients diagnosed with myocardial infarction between October 2015 and May 2016.The

磁共振钆靶向对比剂的研究现状及展望

特异性MR靶向对比剂通过与体内特定的靶点结合显示活体分子靶点状态,为临床提供分子水平的信息。选择针对特定靶点的特异性运载体和良好的MR显像剂,是构建良好分子探针的一个关键因素。钆剂作为临床常用的MR对比剂,在构建分子探针上具有诸多优势,目前在MR分子成像领域进行了大量实验研究。就目前研究常用的分子靶点和分子探针,对MR钆靶向对比剂的研究现状及展望进行综述。

Characteristics of magnetic Fe_3O_4 nanoparticles encapsulated with human serum albumin

Magnetic nanoparticles （Fe304） were prepared by chemical precipitation method using Fe^2＋ and Fe^3＋ salts with sodium hydroxide in the nitrogen atmosphere. Fe3O4 nanoparticles were coated with human serum albumin（HSA） for magnetic resonance imaging as contrast agent. Characteristics of magnetic particles coated or uncoated were carried out using scanning electron microscopy and X-ray diffraction. Zeta potentials, package effects and distributions of colloid particles were measured to confirm the attachment of HSA on magnetic particles. Effects of Fe3O4 nanoparticles coated with HSA on magnetic resonance imaging were investigated with rats. The experimental results show that the adsorption of HSA on magnetic particles is very favorable to dispersing of magnetic Fe3O4 particles, while the sizes of Fe3O4 particles coated are related to the molar ratio of Fe3O4 to HSA. The diameters of the majority of particles coated are less than 100 nm. Fe3O4 nanoparticle coated with HSA has a good biocompatibility and low toxicity. This new contrast agent has some effects on the nuclear magnetic resonance imaging of liver and the lowest dosage is 20μmol/kg for the demands of diagnosis.

Cell-assembled （Gd-DOTA）i-triphenylphosphonium （TPP） nanoclusters as a T2 contrast agent reveal in vivo fates of stem cell transplants

A simple and straightforward strategy for magnetic resonance imaging （MRI） of stem cell transplants in terms of their viability, migration and homing, and differentiation has been pursued over the years. Herein we couple Gd-DOTA with triphenylphosphonium （TPP） to yield small molecule （Gd-DOTA）i-TPP （i = 1,4） agents and show that labeling cells with （Gd-DOTA）i-TPP via electro- poration （EP） results in two distinct cellular distributions of （Gd-DOTA）i-TPP： freely and evenly distributed in the cytosol or cell-assembled nanoclusters in the cytoplasm. The two distinct cellular distributions contribute in different ways to MRI signals in vitro and in vivo. Importantly, we present a detailed interpretation of MRI results based on the signal intensity equation and cellular longitudinal （T1-） and transverse （Ta-） relaxation rates of water protons. We demonstrate that cell-assembled （Gd-DOTA）i-TPP nanoclusters not only promote its intracellular retention time but also induce significant MRI signal reduction, which act as an excellent T2 contrast agent and allows for unambiguous reporting of in vivo viability and migration of cell transplants under T2-weighted MRI over a long period. Notably,（Gd-DOTA）i-TPP agents released as a result of exocytosis or cell death induce signal enhancement in the surrounding tissue such that the labeled cells can be unambiguously discriminated from its host tissue. The labeling and imaging strategy provides abundant information on the in vivo fates of stem cell transplants. The strategy features a single contrast, single imaging mode with dual signal output.

Fabrication of carbon coated gadolinia particles for dual-mode magnetic resonance and fluorescence imaging

In the present study,we report a fabrication of dual-mode carbon coated gadolinia C@Gd_(2)O_(3)particles by a facile hydrothermal synthesis method without using any organic solvents.The prepared C@Gd_(2)O_(3)particles have a core-shell structure and a narrow size distribution in the range of 261±27 nm.The fluorescent properties of the prepared C@Gd_(2)O_(3)particles were accessed by a room-temperature photoluminescence study,while the longitudinal relaxivity(r1)was examined by using a clinical 1.5 T MRI scanner.A murine fibroblast L-929 cell line was used to examine the cytotoxicity and capability of the prepared C@Gd_(2)O_(3)particles for the fluorescent labeling.The obtained results show that the prepared C@Gd_(2)O_(3)particles could be used as a dual-mode contrast agent for magnetic resonance and fluorescence imaging.