Commercial Contrast Research Articles

Nanosized T1 MRI Contrast Agent Based on a Polyamidoamine as Multidentate Gd Ligand.

A linear polyamidoamine (PAA) named BAC-EDDS, containing metal chelating repeat units composed of two tert-amines and four carboxylic groups, has been prepared by the aza-Michael polyaddition of ethylendiaminodisuccinic (EDDS) with 2,2-bis(acrylamido)acetic acid (BAC). It was characterized by size exclusion chromatography (SEC), FTIR, UV–Vis and NMR spectroscopies. The pKa values of the ionizable groups of the repeat unit were estimated by potentiometric titration, using a purposely synthesized molecular ligand (Agly-EDDS) mimicking the structure of the BAC-EDDS repeat unit. Dynamic light scattering (DLS) and ζ-potential analyses revealed the propensity of BAC-EDDS to form stable nanoaggregates with a diameter of approximately 150 nm at pH 5 and a net negative charge at physiological pH, in line with an isoelectric point <2. BAC-EDDS stably chelated Gd (III) ions with a molar ratio of 0.5:1 Gd (III)/repeat unit. The stability constant of the molecular model Gd-Agly-EDDS (log K = 17.43) was determined as well, by simulating the potentiometric titration through the use of Hyperquad software. In order to comprehend the efficiency of Gd-BAC-EDDS in contrasting magnetic resonance images, the nuclear longitudinal (r1) and transverse (r2) relaxivities as a function of the externally applied static magnetic field were investigated and compared to the ones of commercial contrast agents. Furthermore, a model derived from the Solomon–Bloembergen–Morgan theory for the field dependence of the NMR relaxivity curves was applied and allowed us to evaluate the rotational correlation time of the complex (τ = 0.66 ns). This relatively high value is due to the dimensions of Gd-BAC-EDDS, and the associated rotational motion causes a peak in the longitudinal relaxivity at ca. 75 MHz, which is close to the frequencies used in clinics. The good performances of Gd-BAC-EDDS as a contrast agent were also confirmed through in vitro magnetic resonance imaging experiments with a 0.2 T magnetic field.

Engineering and quantification of bismuth nanoparticles as targeted contrast agent for computed tomography imaging in cellular and animal models

Bismuth nanoparticles (Bi-NPs) are developed for use as computed tomography (CT) contrast agents (CAs). Herein, the dopamine (DOPA) coated Bi-NPs were synthesized and further functionalized with polyethylene glycol and MUC-16 aptamer (Bi-DOPA-PEG-I-MUC16 NPs). Outside the physicochemical characteristics, in vitro cytotoxicity of Bi-NPs was determined in HeLa and CHO cell lines. The contrast to noise ratio (CNR) effect and figure of merit (FOM) were evaluated at different exposure factors in phantom and cellular tests. Furthermore, the in vivo biodistribution of CAs was investigated by CT imaging and inductively coupled plasma mass spectrometry (ICP-MS) in different organs of rats. The CT number and CNR of Bi-NPs was 8.9 and 13 folds higher, respectively than the commercial CA at equivalent concentrations and similar radiation parameters. With increasing tube current (mA) and tube voltage (kVp), the FOM increased, and conversely, the kVp, CT-values, and CNR was reduced. In vitro results have revealed that the MUC-16 aptamer-targeted Bi-NPs have a 6-fold higher X-ray attenuation ratio than non-targeted Bi-NPs. In vivo results highlighted that synthesized NPs significantly enhance the CT-value and CNR more than iodine-based contrast. These findings have suggested the MUC-16 aptamer targeted NPs as promising targeted CT contrast agents for molecular imaging.

Super stable water-based magnetic fluid as a dual-mode contrast agent

Abstract Early diagnosis of cancer has become one of the effective ways to prevent and treat cancer. At present, magnetic resonance imaging (MRI) diagnosis based on nanosized iron oxide with no toxicity and excellent biocompatibility has attracted much attention. But the poor stability of magnetic fluid (MF) is becoming more and more prominent. In view of the poor stability of MF, the dodecanethiol-poly(methacrylic acid) (DDT-PMAA) as an outer shell was prepared for the MFs (Fe3O4@DDT-PMAA MF) to improve the stability. We also compared the amount of reactants, the ratio of reactants, and the reaction temperature, and finally screened out the best reaction conditions, so as to get more stable products. The stability of the system was studied by visual observation, stability index (I), and magnetic weight change. The results demonstrated that Fe3O4@DDT-PMAA can be stable for more than 60 days. The T 1 mapping image showed that the longitudinal relaxivity (r 1) value was 6.9 mM−1 s−1 (1.5 T, room temperature), which was higher than the commercial contrast agent SHU-555 (r 1 = 2.9 mM−1 s−1), but the transverse relaxivity (r 2) value accounted for 64.48% of the commercial contrast agent Feridex (r 2 = 67.8 mM−1 s−1, 1.5 T, room temperature) because the outermost layer was encapsulated by a polymer. In addition, the imaging effect was more vivid and there was almost no background interference of T 1- and T 2-weighted images in vivo, which indicated that the Fe3O4@DDT-PMAA MF exhibited excellent potential in MRI applications.

Polyaspartic Acid-Coated Paramagnetic Gadolinium Oxide Nanoparticles as a Dual-Modal T1 and T2 Magnetic Resonance Imaging Contrast Agent

Surface-coating polymers contribute to nanoparticle-based magnetic resonance imaging (MRI) contrast agents because they can affect the relaxometric properties of the nanoparticles. In this study, polyaspartic acid (PASA)-coated ultrasmall Gd2O3 nanoparticles with an average particle diameter of 2.0 nm were synthesized using the one-pot polyol method. The synthesized nanoparticles exhibited r1 and r2 of 19.1 and = 53.7 s−1mM−1, respectively, (r1 and r2 are longitudinal and transverse water–proton spin relaxivities, respectively) at 3.0 T MR field, approximately 5 and 10 times higher than those of commercial Gd-chelate contrast agents, respectively. The T1 and T2 MR images could be obtained due to an appreciable r2/r1 ratio of 2.80, indicating their potential as a dual-modal T1 and T2 MRI contrast agent.

Re-engineering a Liposome with Membranes of Red Blood Cells for Drug Delivery and Diagnostic Applications.

Red blood cells (RBCs) make up the overwhelming majority of cells in the vascular system, spending most of their lives wandering the vast network of vessels that permeate every tissue of our bodies. Therefore, the delivery of any class of therapeutic agent that must stay in the circulatory system may benefit from being carried by RBCs. Toward this direction, we have re-engineered a synthetic liposome with the membranes of RBCs and incorporated a magnetic resonance imaging (MRI) contrast agent gadolinium along with the chemotherapeutic drug doxorubicin (DOX) to form a biomimetic liposome (BML). The BMLs proposed herein consist of biocompatible/biodegradable synthetic phospholipids, which include 1,2-distearoyl-sn-glycero-3-phosphoglycerol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and gadolinium-conjugated lipids. These synthetic phospholipids have been fused with a natural RBC membrane and are loaded with DOX using the extrusion technique. BMLs were characterized for their physicochemical properties, stability, fusogenic (between synthetic and natural lipid from RBC), magnetic, drug loading, biocompatibility, and cytotoxicity properties. BMLs had a hydrodynamic diameter of 180 ± 20 nm with a negative surface charge of 29 ± 2 mV. The longitudinal relaxivity (r1) of BML is 3.71 mM-1 s-1, which is comparable to the r1 of commercial contrast agent, Magnevist. In addition, DOX-loaded BML showed a cytotoxicity pattern similar to that of free DOX. These results showed the potential of using the proposed BML system for both MRI-based diagnostic applications and drug delivery platforms.

Holmium(III) Single-Ion Magnet for Cryomagnetic Refrigeration Based on an MRI Contrast Agent Derivative.

The coexistence of field-induced blockage of the magnetization and significant magnetocaloric effects in the low-temperature region occurs in a mononuclear holmium(III) diethylenetriamine-N,N,N′,N″,N″-pentaacetate complex, whose gadolinium(III) analogue is a commercial MRI contrast agent. Both properties make it a suitable candidate for cryogenic magnetic refrigeration, thus enlarging the variety of applications of this simple class of multifunctional molecular nanomagnets.

Porphyrin-Based Tumor-Targeting Theranostic Agent: Gd-TDAP.

The aim of this work was to evaluate a tumor-targeting porphyrin-based gadolinium complex (Gd-TDAP) for use as an MR/optical imaging agent and potential therapeutic agent. Gd-TDAP had higher longitudinal relaxivity (11.8 mM-1 s-1) than a commercial MRI contrast agent (Omniscan; 3.7 mM-1 s-1) in HSA solution (0.67 mM) at 3 T. The tumor-targeting characteristics were confirmed by T1-weighted MR imaging and optical imaging using an orthotopic brain tumor mouse model, which showed 1.3-fold higher uptake in tumor compared to normal brain tissues. The cell fraction data using U87MG glioblastoma cells indicated the potential for gadolinium neutron capture therapy (Gd-NCT), which requires gadolinium to be inside the cell nucleus. In addition, porphyrin derivatives can be used for photodynamic therapy (PDT), and the results demonstrated that Gd-TDAP has great potential not only as a bimodal imaging agent but also for treatment.

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Effect of Acoustic Parameters and Microbubble Concentration on the Likelihood of Encapsulated Microbubble Coalescence

Microbubble contrast agents are commonly used for therapeutic and diagnostic imaging applications. Under certain conditions, these contrast agents can coalesce on ultrasound application and form larger bubbles than the initial population. The formation of large microbubbles potentially influences therapeutic outcomes and imaging quality. We studied clinically relevant ultrasound parameters related to low-pressure therapy and contrast-enhanced ultrasound imaging to determine their effect on microbubble coalescence and subsequent changes in microbubble size distributions in vitro. Results indicate that therapeutic ultrasound at low frequencies, moderate pressures and high duty cycles are capable of forming bubbles greater than two times larger than the initial bubble distribution. Furthermore, acoustic parameters related to contrast-enhanced ultrasound imaging that are at higher frequency, low-pressure and low-duty cycle exhibit no statistically significant changes in bubble diameter, suggesting that standard contrast ultrasound imaging does not cause coalescence. Overall, this work suggests that the microbubble coalescence phenomenon can readily occur at acoustic parameters used in therapeutic ultrasound, generating bubbles much larger than those found in commercial contrast agents, although coalescence is unlikely to be significant in diagnostic contrast-enhanced ultrasound imaging. This observation warrants further expansion of parameter ranges and investigation of resulting effects.

Preparation and properties of bifunctional Gd2O3/GQD composite nanoparticles

Nanocomposites of graphene quantum dots (GQDs) modified gadolinium oxide (Gd2O3) particles were successfully synthesized. In addition, the effects of the amount of GQDs and the particle size of Gd2O3 on the properties of nanocomposites were investigated. The structures and properties of nanoparticles were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, photoluminescence spectrometry, and magnetic resonance imaging. The results show that the synthesized particles Gd2O3/GQD are spherical with a diameter of approximately 40 nm and have excellent fluorescence and magnetic property, and its relaxation rate (r1 = 25.18 (mmol/L)−1/s) is higher than that of the typical commercial contrast agents Gd-DTPA (r1 = 4.5 (mmol/L)−1/s). The fluorescence property of Gd2O3/GQD is optimized by varying the VGQDs:VGd2O3 ratio, and 1:1 ratio of VGQDs:VGd2O3 results in the best fluorescence property. The large particles of Gd2O3 improve the relaxation property of nanocomposites. Therefore, the nanocomposites Gd2O3/GQD with magnetic and fluorescence characteristics can be used in biological imaging, drug targeting, and in-vivo diagnostic analysis.

Graphene Quantum Dots Co-Doped with Nitrogen/Mn(II) or Nitrogen/Gd(III) for Bimodal Magnetic Resonance and Fluorescence Imaging

Graphene quantum dots (GQDs) are unique derivatives of graphene that show promise in multiple biomedical applications as biosensors, bioimaging agents, and drug/gene delivery vehicles. Their ease in functionalization, biocompatibility, and intrinsic fluorescence enable those modalities. However, GQDs lack deep tissue magnetic resonance imaging (MRI) capabilities desirable for diagnostics. Considering that the drawbacks of MRI contrast agent toxicity are still poorly addressed, we develop novel Mn2+ or Gd3+ doped nitrogen-containing graphene quantum dots (NGQDs) to equip the GQDs with MRI capabilities and at the same time render contrast agents biocompatible. Water-soluble biocompatible Mn-NGQDs and Gd-NGQDs synthesized via single-step microwave-assisted scalable hydrothermal reaction enable dual MRI and fluorescence modalities. These quasi-spherical 3.9–6.6 nm average-sized structures possess highly crystalline graphitic lattice structure with 0.24 and 0.53 atomic % for Mn2+ and Gd3+ doping. This structure ensures high in vitro biocompatibility of up to 1.3 mg ml−1 and 1.5 mg ml−1 for Mn-NGQDs and Gd-NGQDs, respectively, and effective internalization in HEK-293 cells traced by intrinsic NGQD fluorescence. As MRI contrast agents with considerably low Gd and Mn content, Mn-NGQDs exhibit substantial transverse/longitudinal relaxivity (r 2/r 1) ratios of 11.190, showing potential as dual-mode longitudinal or transverse relaxation time (T 1 or T 2) contrast agents, while Gd-NGQDs possess r 2/r 1 of 1.148 with high r 1 of 9.546 mM−1 s−1 compared to commercial contrast agents, suggesting their potential as T1 contrast agents. Compared to other nanoplatforms, these novel Mn2+ and Gd3+ doped NGQDs not only provide scalable biocompatible alternatives as T1/T2 and T1 contrast agents but also enable in vitro intrinsic fluorescence imaging.

Tetraphenylethylene-conjugated polycation covered iron oxide nanoparticles for magnetic resonance/optical dual-mode imaging.

Magnetic resonance (MR)/optical dual-mode imaging with high sensitivity and high tissue resolution have attracted many attentions in biomedical applications. To avert aggregation-caused quenching of conventional fluorescence chromophores, an aggregation-induced emission molecule tetraphenylethylene (TPE)-conjugated amphiphilic polyethylenimine (PEI) covered superparamagnetic iron oxide (Alkyl-PEI-LAC-TPE/SPIO nanocomposites) was prepared as an MR/optical dual-mode probe. Alkyl-PEI-LAC-TPE/SPIO nanocomposites exhibited good fluorescence property and presented higher T2 relaxivity (352 Fe mM−1s−1) than a commercial contrast agent Feridex (120 Fe mM−1s−1) at 1.5 T. The alkylation degree of Alkyl-PEI-LAC-TPE effects the restriction of intramolecular rotation process of TPE. Reducing alkane chain grafting ratio aggravated the stack of TPE, increasing the fluorescence lifetime of Alkyl-PEI-LAC-TPE/SPIO nanocomposites. Alkyl-PEI-LAC-TPE/SPIO nanocomposites can effectively labelled HeLa cells and resulted in high fluorescence intensity and excellent MR imaging sensitivity. As an MR/optical imaging probe, Alkyl-PEI-LAC-TPE/SPIO nanocomposites may be used in biomedical imaging for certain applications.

Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging

The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1−3 h, which was considerably longer than that observed with iopamidol and sAu/GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.

Ultrasound-sensitive nanodroplets achieve targeted neuromodulation

Focused ultrasound (FUS) offers an attractive tool for non-invasive neuromodulation, addressing a clinical need to develop more minimally invasive approaches that are safer, more tolerable and versatile. In combination with a cavitation agent, the effects of ultrasound can be amplified and localized for therapy. Using c-Fos expression mapping, we show how ultrasound-sensitive nanodroplets can be used to induce either neurosuppression or neurostimulation, without disrupting the blood-brain barrier in rats. By repurposing a commercial ultrasound contrast agent, Definity, lipid-shell decafluorobutane-core nanodroplets of 212.5 ± 2.0 nm were fabricated and loaded with or without pentobarbital. FUS was delivered with an atlas-based targeting system at 1.66 MHz to the motor cortex of rats, using a feedback-controller to detect successful nanodroplet vaporization and drug release. Neuromodulation was quantified through changes in sensorimotor function and c-Fos expression. Following FUS-triggered delivery, sham nanodroplets induced a 22.6 ± 21% increase in local c-Fos expression, whereas pentobarbital-loaded nanodroplets induced a 21.7 ± 13% decrease (n = 6). Nanodroplets, combined with FUS, offer an adaptable tool for neuromodulation, through local delivery of small molecule anesthetics or targeted mechanical effects.

Hydrophilic Biocompatible Poly(Acrylic Acid-co-Maleic Acid) Polymer as a Surface-Coating Ligand of Ultrasmall Gd2O3 Nanoparticles to Obtain a High r1 Value and T1 MR Images.

The water proton spin relaxivity, colloidal stability, and biocompatibility of nanoparticle-based magnetic resonance imaging (MRI) contrast agents depend on the surface-coating ligands. Here, poly(acrylic acid-co-maleic acid) (PAAMA) (Mw = ~3000 amu) is explored as a surface-coating ligand of ultrasmall gadolinium oxide (Gd2O3) nanoparticles. Owing to the numerous carboxylic groups in PAAMA, which allow its strong conjugation with the nanoparticle surfaces and the attraction of abundant water molecules to the nanoparticles, the synthesized PAAMA-coated ultrasmall Gd2O3 nanoparticles (davg = 1.8 nm and aavg = 9.0 nm) exhibit excellent colloidal stability, extremely low cellular toxicity, and a high longitudinal water proton spin relaxivity (r1) of 40.6 s−1mM−1 (r2/r1 = 1.56, where r2 = transverse water proton spin relaxivity), which is approximately 10 times higher than those of commercial molecular contrast agents. The effectiveness of PAAMA-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent is confirmed by the high positive contrast enhancements of the in vivo T1 MR images at the 3.0 T MR field.

Manganese–nitrogen and gadolinium–nitrogen Co-doped graphene quantum dots as bimodal magnetic resonance and fluorescence imaging nanoprobes

Graphene quantum dots (GQDs) are unique derivatives of graphene that show promise in multiple biomedical applications as biosensors, bioimaging agents, and drug/gene delivery vehicles. Their ease in functionalization, biocompatibility, and intrinsic fluorescence enable those modalities. However, GQDs lack deep tissue magnetic resonance imaging (MRI) capabilities desirable for diagnostics. Considering that the drawbacks of MRI contrast agent toxicity are still poorly addressed, we develop novel Mn2+ or Gd3+ doped nitrogen-containing graphene quantum dots (NGQDs) to equip the GQDs with MRI capabilities and at the same time render contrast agents biocompatible. Water-soluble biocompatible Mn-NGQDs and Gd-NGQDs synthesized via single-step microwave-assisted scalable hydrothermal reaction enable dual MRI and fluorescence modalities. These quasi-spherical 3.9–6.6 nm average-sized structures possess highly crystalline graphitic lattice structure with 0.24 and 0.53 atomic % for Mn2+ and Gd3+ doping. This structure ensures high in vitro biocompatibility of up to 1.3 mg ml−1 and 1.5 mg ml−1 for Mn-NGQDs and Gd-NGQDs, respectively, and effective internalization in HEK-293 cells traced by intrinsic NGQD fluorescence. As MRI contrast agents with considerably low Gd and Mn content, Mn-NGQDs exhibit substantial transverse/longitudinal relaxivity (r 2/r 1) ratios of 11.190, showing potential as dual-mode longitudinal or transverse relaxation time (T 1 or T 2) contrast agents, while Gd-NGQDs possess r 2/r 1 of 1.148 with high r 1 of 9.546 mM−1 s−1 compared to commercial contrast agents, suggesting their potential as T1 contrast agents. Compared to other nanoplatforms, these novel Mn2+ and Gd3+ doped NGQDs not only provide scalable biocompatible alternatives as T1/T2 and T1 contrast agents but also enable in vitro intrinsic fluorescence imaging.

A positively charged small-molecule T1 magnetic resonance imaging contrast agent for highly efficient labeling and tracking adipose tissue-derived stem cells

Stem cells have great promise in regenerative medicine, and in vivo visualization of transplanted stem cells with noninvasive technique is essential for tracking and monitoring cell behaviors. Herein, a small-molecule T1 contrast agent with positive charge was prepared for efficiently labeling adipose-derived stem cells (ADSCs) in vitro and in vivo. The contrast agent was synthesized by conjugating quaternary ammonium salt onto DO3A (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7-triacetic acid) skeleton via nucleophilic reaction, then chelating gadolinium ion to form Gd-HP-DO3A-TA complex. The Gd-HP-DO3A-TA exhibited a similar longitudinal relaxivity (4.42 mM−1 s−1) as commercial contrast agent (Gd-DTPA), but it can be efficiently internalized by ADSCs, leading to remarkably enhanced cellular magnetic resonance imaging (MRI) signal intensity without negative effects on viability, proliferation and multi-differentiation potential of ADSCs. Moreover, in vivo experiments revealed that Gd-HP-DO3A-TA-labeled ADSCs can home to the injured liver region with enhanced signal contrast and promote to rebuild liver function. Our results indicate that the small-molecule T1 contrast agent with positive charge has great potential for stem cells labeling and MRI tracking.

Ultrasensitive iron-based magnetic resonance contrast agent constructed with natural polyphenol tannic acid for tumor theranostics

Because of the toxicity of Gd(III) complexes and the poor T1 magnetic resonance imaging (MRI) contrast of superparamagnetic iron oxide, the development of new stable, non-toxic, and efficient contrast agents is desirable. Herein, tannic acid (TA), a large natural polyphenol, and bovine serum albumin (BSA) were used to construct non-toxic Fe(III) complexes with increased relaxivity based on a strategy slowing the molecular spin. Compared with the commercial T1 contrast agent Magnevist, TA-Fe@BSA not only exhibits comparable T1 MRI contrast enhancement under 0.5, 1 and 7 T magnetic fields both in vitro and in vivo, but also has better stability and biocompatibility. Moreover, TA-Fe@BSA with near-infrared (NIR) absorption demonstrates efficient tumor ablation via photothermal effects. These results demonstrate their strong potential as an alternative T1 MRI contrast agent and tumor theranostics agent in clinical settings.

Coordination-Assembled Water-Soluble Anionic Lanthanide Organic Polyhedra for Luminescent Labeling and Magnetic Resonance Imaging.

Lanthanide-containing functional complexes have found a variety of applications in materials science and biomedicine because of their unique electroptical and magnetic properties. However, the poor stability and solubility in water of multicomponent lanthanide organic assemblies significantly limit their practical applications. We report here a series of water-stable anionic Ln2nL3n-type (n = 2, 3, 4, and 5) lanthanide organic polyhedra (LOPs) constructed by deprotonation self-assembly of three fully conjugated ligands (H4L1 and H4L2a/b) featuring a 2,6-pyridine bitetrazolate chelating moiety. The outcomes of the LOPs formation reactions were found to be very sensitive toward the reaction conditions including base, metal source, solvents, and concentrations as characterized by a combination of NMR, high-resolution ESI-MS and X-ray crystallography. Ligands H4L2a/b manifested an excellent sensitization toward lanthanide ions (Ln = EuIII and TbIII), with high luminescent quantum yields for Tb8L2a12 (Φ = 11.2% in water) and Eu8L2b12 (Φ = 76.8% in DMSO) measured in polar solvents. Furthermore, due to the giant molecular weight and rigidity of the polyhedral skeleton, Gd8L2b12 showed a very high longitudinal relaxivity (r1) of 400.53 mM-1S-1. The performance of Gd8L2b12 as potential magnetic resonance imaging contrast agents (CAs) in vivo was evaluated with much longer retention time in the tumor sites compared with the commercial GdIII-based CAs. Dual-modal imaging potential has also been demonstrated with the mixed Eu/Gd LOPs. Our results not only provide a new design route toward water-stable multinuclear lanthanide organic assemblies but also offer potential candidates of supramolecular-edifices for bioimaging and drug delivery.

Development of composite nanoparticles composed of silica-coated nanorods and single nanometer-sized gold particles toward a novel X-ray contrast agent

Gold (Au) is expected to function as a high contrast agent for X-ray computed tomography imaging as it has high X-ray absorptivity owing to a large atomic number compared to commercial materials such as barium and iodine. In addition, Au formation with a nanorod structure (AuNR) can be used for hyperthermia because of the enhancement of the photothermal reaction effect. The present work proposes a preparation method for core–shell nanoparticles composed of AuNR, SiO2, and a single nanometer-sized Au (sAu), toward imaging and photothermal therapy. The AuNRs (lateral size: 12.6 nm; longitudinal size: 44.9 nm) were silica-coated using a sol–gel method with tetraethyl orthosilicate, which produced AuNR/SiO2 nanoparticles with an average size of 86.9 nm. Thiol groups were introduced onto the AuNR/SiO2 nanoparticle surface by using (3-mercaptopropyl) trimethoxysilane (AuNR/SiO2-SH). The sAu nanoparticles (particle size: 2.6 nm) were produced by adding tetrakis (hydroxymethyl) phosphonium chloride as a reductant and HAuCl4 (aq) to NaOH solution. A thiol-terminated PEG (PEG-SH) aqueous solution and sAu nanoparticle colloidal solution were added in turn to the AuNR/SiO2-SH dispersed in EtOH (AuNR/SiO2/sAu-PEG). The CT value of the AuNR/SiO2/sAu-PEG particle solution was 702 HU. The CT values in tissues immediately increased after injection into mouse. Their blood retention times were 3–6 h, much longer than the few minutes of a commercial X-ray contrast agent (Iopamiron).