MR Relaxivity Research Articles

Fluorescent Probes Based on AIEgen‐Mediated Polyelectrolyte Assemblies for Manipulating Intramolecular Motion and Magnetic Relaxivity

AbstractUniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity‐driven assembling strategy not only restricts the intramolecular motion‐induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation‐induced emission luminogen (AIEgen)‐mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique “soft” inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio‐temporal MRI‐guided high‐efficient PTT.

Fluorescent Probes Based on AIEgen-Mediated Polyelectrolyte Assemblies for Manipulating Intramolecular Motion and Magnetic Relaxivity.

Uniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity-driven assembling strategy not only restricts the intramolecular motion-induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation-induced emission luminogen (AIEgen)-mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique "soft" inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio-temporal MRI-guided high-efficient PTT.

One-pot synthesis of carboxymethyl-dextran coated iron oxide nanoparticles (CION) for preclinical fMRI and MRA applications

Superparamagnetic iron-oxide nanoparticles are robust contrast agents for magnetic resonance imaging (MRI) used for sensitive structural and functional mapping of the cerebral blood volume (CBV) when administered intravenously. To date, many CBV-MRI studies are conducted with Feraheme, manufactured for the clinical treatment of iron-deficiency. Unfortunately, Feraheme is currently not available outside the United States due to commercial and regulatory constraints, making CBV-MRI methods either inaccessible or very costly to achieve. To address this barrier, we developed a simple, one-pot recipe to synthesize Carboxymethyl-dextran coated Iron Oxide Nanoparticles, namely, “CION”, suitable for preclinical CBV-MRI applications. Here we disseminate a step-by-step instruction of our one-pot synthesis protocol, which allows CION to be produced in laboratories with minimal cost. We also characterized different CION-conjugations by manipulating polymer to metal stoichiometric ratio in terms of their size, surface chemistry, and chemical composition, and shifts in MR relaxivity and pharmacokinetics. We performed several proof-of-concept experiments in vivo, demonstrating the utility of CION for functional and structural MRI applications, including hypercapnic CO2 challenge, visual stimulation, targeted optogenetic stimulation, and microangiography. We also present evidence that CION can serve as a cross-modality research platform by showing concurrent in vivo optical and MRI measurement of CBV using fluorescent-labeled CION. The simplicity and cost-effectiveness of our one-pot synthesis method should allow researchers to reproduce CION and tailor the relaxivity and pharmacokinetics according to their imaging needs. It is our hope that this work makes CBV-MRI more openly available and affordable for a variety of research applications.

Ultrathin Transition Metal Chalcogenide Nanosheets Synthesized via Topotactic Transformation for Effective Cancer Theranostics.

Ultrathin transition metal chalcogenide (TMC) nanosheets with ultrahigh photothermal conversion efficiency (η) and excellent stability are strongly desired in the application of photothermal therapy (PTT). However, the current synthetic methods of ultrathin TMC nanosheets have issues in obtaining uniform morphology, good dispersion, and satisfactory PTT behavior. Herein, ultrathin nanosheets of CoFe-selenide (CFS) with a finely controlled structure were prepared via a topological structural transformation process from an ultrathin CoFe-layered double hydroxide (LDH) precursor, followed by surface modification with poly(ethylene glycol) (PEG). The as-prepared CFS-PEG nanosheets inherit the ultrathin morphology of CoFe-LDH and exhibit an outstanding photothermal performance with a η of 74.5%, which is the first rank level of reported two-dimensional (2D) TMC nanosheet materials. The CFS-PEG nanosheets possess a satisfactory photoacoustic (PA) imaging capability with an ultralow detection limit (5 ppm) and simultaneously superior T2 magnetic resonance imaging (MRI) performance with a large transverse MR relaxivity value (r2) of 347.7 mM-1 s-1. Moreover, in vitro and in vivo assays verify superior anticancer activity with a dramatic photoinduced cancer cell apoptosis and tumor ablation. Therefore, a successful paradigm is provided for rational design and preparation of ultrathin TMC nanosheets in this work, holding enormous potential in cancer theranostics.

CT/MR Dual-Modality Imaging Tracking of Mesenchymal Stem Cells Labeled with a Au/GdNC@SiO2 Nanotracer in Pulmonary Fibrosis.

Mesenchymal stem cells (MSCs) have shown potential as an innovative treatment for pulmonary fibrosis (PF), due to their capability to ameliorate the inflammation and moderate the deterioration of PF. The fate of the stem cells transplanted into the lung, including survival, migration, homing, and functions, however, has not been fully understood yet. In this paper, we report the development of a computed tomography/magnetic resonance (CT/MR) dual-modal nanotracer, gold/gadolinium nanoclusters overcoated with a silica shell (Au/GdNC@SiO2), for noninvasive labeling and tracking of the transplanted human MSCs (hMSCs) in a PF model. The Au/GdNC@SiO2 nanotracer exhibits good colloidal and chemical stability, high biocompatibility, enhanced longitudinal MR relaxivity, and superior X-ray attenuation property. The hMSCs can be effectively labeled with Au/GdNC@SiO2, resulting in a significantly increased cellular CT/MR imaging contrast, without any obvious adverse effect on the function, including proliferation and differentiation of the labeled stem cells. Moreover, by using the Au/GdNC@SiO2 nanotracer, the hMSCs transplanted in the lung can be tracked for 7 d via in vivo CT/MR dual-modality imaging. This work may provide an insight into the role the transplanted hMSCs play in PF therapy, thus promoting the stem cell-based regenerative medicine.

Magnetic Nanoparticles Supporting Bio-responsive T1/T2 Magnetic Resonance Imaging.

The use of nanoparticulate systems as contrast agents for magnetic resonance imaging (MRI) is well-established and known to facilitate an enhanced image sensitivity within scans of a particular pathological region of interest. Such a capability can enable both a non-invasive diagnosis and the monitoring of disease progression/response to treatment. In this review, magnetic nanoparticles that exhibit a bio-responsive MR relaxivity are discussed, with pH-, enzyme-, biomolecular-, and protein-responsive systems considered. The ability of a contrast agent to respond to a biological stimulus provides not only enriched diagnostic capabilities over corresponding non-responsive analogues, but also an improved longitudinal monitoring of specific physiological conditions.

Synthesis, MR Relaxivities, and In Vitro Cytotoxicity of 3,5-Diiodo-L-tyrosine-Coated Gd2O3 Nanoparticles

In this study, we report the synthesis and characterization of 3,5-Diiodo-L-tyrosine (DLT)-coated gadolinium oxide (Gd2O3) nanoparticles. The bonding status of DLT-coated Gd2O3 nanoparticles (DLT-NPs) were confirmed by Fourier transform infrared (FT-IR) absorption spectra and thermogravimetric analysis (TGA). The surface coating amount was estimated to be 73% in weight percent from a TGA. High-resolution transmission electron microscope (HR-TEM) shows that DLT-NPs were spherical in shape with an average diameter 2 nm. The MR relaxivity measurements confirmed that the DLT-NPs have higher r1 = 9.24 s-1 mM-1 than commercially available contrast agents. Furthermore, the bio-compatibility of the DLT-NPs were measured by cytotoxicity test, which has demonstrated that the cell viability reached up to 60% with Gd concentrations up to 50 μM for both DU145 and NCTC1469 cell lines, making them a promising candidate for biomedical applications.

Effect of Mesoporous Nano Water Reservoir on MR Relaxivity

In the present work, an attempt was made to engineer a mesoporous silica coated magnetic nanoparticles (MNF@mSiO2) for twin mode contrast in magnetic resonance imaging (MRI) with reduced toxicity. Superparamagnetic manganese ferrite nanoparticles were synthesized with variable mesoporous silica shell thickness to control the water molecules interacting with metal oxide core. 178 nm was the optimum hydrodynamic diameter of mesoporous ferrite core-shell nanoparticles that showed maximum longitudinal relaxation time (T1) and transverse relaxation time (T2) in MRI due to the storage of water molecules in mesoporous silica coating. Besides the major role of mesoporous silica in controlling relaxivity, mesoporous silica shell also reduces the toxicity and enhances the bioavailability of superparamagnetic manganese ferrite nanoparticles. The in vitro toxicity assessment using HepG2 liver carcinoma cells shows that the mesoporous silica coating over ferrite nanoparticles could exert less toxicity compared to the uncoated particle.

Structure-Dependent Antimicrobial Theranostic Functions of Self-Assembled Short Peptide Nanoagents.

Gadolinium (Gd[III])-based nanoaggregates are potential noninvasive magnetic resonance imaging (MRI) probes with excellent spatial and temporal resolution for cancer diagnosis. Peptides conjugated with Gd3+ can aid in supramolecular scaffolding for MRI nanoagents because of their inherent biocompatibility and degradability. We report here a strategy to tune the MR relaxivity of tumor cell-targeted nanoagents and enhance the antimicrobial and anticancer activities of nanoagents based on rationally designed antimicrobial peptide (AMP) assembly. A tripeptide with glycyl-l-histidyl-l-lysine (GHK) capable of Gd3+ chelation was attached to short AMPs containing pyrazole amino acids that spontaneously assembled as a function of the number of hydrophobic amino acid residues and the peptide length of AMPs. Aqueous coassembly of GHK with tumor-targeting, cyclic arginine-glycine-aspartic acid (cRGD)-tagged AMPs resulted in the formation of micelles, fibrils, vesicles, sheets, and planar networks. Interestingly, the two-dimensional planar network nanostructure showed less antibacterial activity and tumor cell cytotoxicity but greater drug loading/delivery and magnetic resonance signaling than micelles because of its intrinsic structural characteristics. This study can provide a rational approach for the design and fabrication of clinically useful nanoagents.

Ultrasmall Superparamagnetic Iron Oxide Nanoparticle for T2-Weighted Magnetic Resonance Imaging.

A facile method to synthesize ultrasmall-sized supermagnetic iron oxide nanoparticles with good monodispersity and high relaxivity is desired for magnetic resonance imaging (MRI) technology. Herein, we have developed a one-step method to direct the formation of superparamagnetic iron oxide nanoparticle (uBSPIO) using albumin under mild conditions. The resulting uBSPIO possess ultrasmall size (4.78 ± 0.55 nm) and super high MR relaxivity (444.56 ± 8.82 mM-1 s-1). After grafted by the luteinizing hormone release hormone peptide (LHRH), the uBSPIO could targeted and accumulated in the tumor site. Finally, the uBSPIOs had good stability and did not induce cytotoxicity in vitro or major organ toxicity in vivo. The uBSPIOs are promising contrast agents for MRI.

Conformational Changes in High-Density Lipoprotein Nanoparticles Induced by High Payloads of Paramagnetic Lipids.

High-density lipoprotein (HDL) nanoparticles doped with gadolinium lipids can be used as magnetic resonance imaging diagnostic agents for atherosclerosis. In this study, HDL nanoparticles with different molar fractions of gadolinium lipids (0 < xGd-lipids < 0.33) were prepared, and the MR relaxivity values (r1 and r2) for all compositions were measured. Both r1 and r2 parameters reached a maximal value at a molar fraction of approximately xGd-lipids = 0.2. Higher payloads of gadolinium did not significantly increase relaxivity values but induced changes in the structure of HDL, increasing the size of the particles from dH = 8.2 ± 1.6 to 51.7 ± 7.3 nm. High payloads of gadolinium lipids trigger conformational changes in HDL, with potential effects on the in vivo behavior of the nanoparticles.

Genetic manipulation of iron biomineralization enhances MR relaxivity in a ferritin-M6A chimeric complex.

Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene – ferritin-M6A – in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation. Ferritin-M6A-expressing C6-glioma cells showed enhanced (per iron) r2 relaxivity. MRI in vivo studies of ferritin-M6A-expressing tumour xenografts showed enhanced R2 relaxation rate in the central hypoxic region of the tumours. Such enhanced relaxivity would increase the sensitivity of ferritin as a reporter gene for non-invasive in vivo MRI-monitoring of cell delivery and differentiation in cellular or gene-based therapies.

PEGylated NaHoF4 nanoparticles as contrast agents for both X-ray computed tomography and ultra-high field magnetic resonance imaging

It is well-known that multimodal imaging can integrate the advantages of different imaging modalities by overcoming their individual limitations. As ultra-high field magnetic resonance imaging (MRI) will be inevitably used in future MRI/X-ray computed tomography (CT) scanner, it is highly expected to develop high-performance nano-contrast agents for ultra-high field MR and CT dual-modality imaging, which has not been reported yet. Moreover, specific behavior of nano-contrast agents for ultra-high field MRI is a challenging work and still remains unknown. Herein, a novel type of NaHoF4 nanoparticles (NPs) with varied particle sizes were synthesized and explored as high-performance dual-modality contrast agents for ultra-high field MR and CT imaging. The specific X-ray absorption and MR relaxivity enhancements with varied nanoparticle diameters (3 nm, 7 nm, 13 nm and 29 nm) under different magnetic field (1.5/3.0/7.0 T) are investigated. Based on experimental results and theoretical analysis, the Curie and dipolar relaxation mechanisms of NaHoF4 NPs are firstly separated. Our results will greatly promote the future medical translational development of the NaHoF4 nano-contrast agents for ultra-high field MR/CT dual-modality imaging applications.

Facile Synthesis of Gd-Cu-In-S/ZnS Bimodal Quantum Dots with Optimized Properties for Tumor Targeted Fluorescence/MR In Vivo Imaging.

Dual-modal imaging techniques have gained intense attention for their potential role in the dawning era of tumor early accurate diagnosis. Chelate-free robust dual-modal imaging nanoprobes with high efficiency and low toxicity are of essential importance for tumor targeted dual-modal in vivo imaging. It is still a crucial issue to endow Cd-free dual-modal nanoprobes with bright fluorescence as well as high relaxivity. Herein, a facile synthetic strategy was developed to prepare Gd-doped CuInS/ZnS bimodal quantum dots (GCIS/ZnS, BQDs) with optimized properties. The fluorescent properties of the GCIS/ZnS BQDs can be thoroughly optimized by varying reaction temperature, aging time, and ZnS coating. The amount of Gd precursor can be well-controlled to realize the optimized balance between the MR relaxivity and optical properties. The obtained hydrophobic GCIS/ZnS BQDs were surface engineered into aqueous phase with PEGylated dextran-stearyl acid polymeric lipid vesicles (PEG-DS PLVs). Upon the phase transfer, the hydrophilic GCIS/ZnS@PLVs exhibited pronounced near-infrared fluorescence as well as high longitudinal relaxivity (r1 = 9.45 mM(-1) S(-1)) in water with good colloidal stability. In vivo tumor-bearing animal experiments further verified GCIS/ZnS@PLVs could achieve tumor-targeted MR/fluorescence dual-modal imaging. No toxicity was observed in the in vivo and ex vivo experiments. The GCIS/ZnS@PLVs present great potential as bimodal imaging contrast agents for tumor diagnosis.

A New Interleukin-13 Amino-Coated Gadolinium Metallofullerene Nanoparticle for Targeted MRI Detection of Glioblastoma Tumor Cells.

The development of new nanoparticles as next-generation diagnostic and therapeutic ("theranostic") drug platforms is an active area of both chemistry and cancer research. Although numerous gadolinium (Gd) containing metallofullerenes as diagnostic magnetic resonance imaging (MRI) contrast agents have been reported, the metallofullerene cage surface, in most cases, consists of negatively charged carboxyl or hydroxyl groups that limit attractive forces with the cellular surface. It has been reported that nanoparticles with a positive charge will bind more efficiently to negatively charged phospholipid bilayer cellular surfaces, and will more readily undergo endocytosis. In this paper, we report the preparation of a new functionalized trimetallic nitride template endohedral metallofullerene (TNT EMF), Gd3N@C80(OH)x(NH2)y, with a cage surface bearing positively charged amino groups (-NH3(+)) and directly compare it with a similar carboxyl and hydroxyl functionalized derivative. This new nanoparticle was characterized by X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), and infrared spectroscopy. It exhibits excellent (1)H MR relaxivity. Previous studies have clearly demonstrated that the cytokine interleukin-13 (IL-13) effectively targets glioblastoma multiforme (GBM) cells, which are known to overexpress IL-13Rα2. We also report that this amino-coated Gd-nanoplatform, when subsequently conjugated with interleukin-13 peptide IL-13-Gd3N@C80(OH)x(NH2)y, exhibits enhanced targeting of U-251 GBM cell lines and can be effectively delivered intravenously in an orthotopic GBM mouse model.

In vivo targeted magnetic resonance imaging and visualized photodynamic therapy in deep-tissue cancers using folic acid-functionalized superparamagnetic-upconversion nanocomposites.

Multifunctional nanoprobes used in magnetic resonance imaging (MRI) and photodynamic therapy (PDT) also have potential applications in diagnosis and visualized therapy of cancers, and hence it is important to investigate the active-targeting ability and in vivo reliability of these nanoprobes. In this work, folic acid (FA)-targeted, photosensitizer (PS)-loaded Fe3O4@NaYF4:Yb/Er (FA-NPs-PS) nanocomposites were synthesized for in vivo T2-weighted MRI and visualized PDT of cancers by modeling MCF-7 tumor-bearing nude mice. By measuring the upconversion luminescence (UCL) and fluorescence emission spectra, the as-prepared FA-NPs-PS nanocomposites showed near-infrared (NIR)-triggered PDT performance due to the production of a singlet oxygen species. Moreover, by tracing PS fluorescence in MCF-7, HeLa cells and in MCF-7 tumors, the FA-targeted nanocomposites demonstrated good targeting ability both in vitro and in vivo. Under the irradiation of a 980 nm laser, the viabilities of MCF-7 and HeLa cells incubated with FA-NPs-PS nanocomposites could decrease to about 18.4% and 30.7%, respectively, and the inhibition of MCF-7 tumors could reach about 94.9%. The transverse MR relaxivity of 63.79 mM(-1) s(-1) (r2 value) and in vivo MR imaging of MCF-7 tumors indicated an excellent T2-weighted MR performance. This work demonstrated that FA-targeted MRI/PDT nanoprobes are effective for in vivo diagnosis and visualized therapy of breast cancers.

Nanostructured magnetic nanocomposites as MRI contrast agents.

Magnetic resonance imaging (MRI) has become an integral part of modern clinical imaging due to its non-invasiveness and versatility in providing tissue and organ images with high spatial resolution. With the current MRI advancement, MRI imaging probes with suitable biocompatibility, good colloidal stability, enhanced relaxometric properties and advanced functionalities are highly demanded. As such, MRI contrast agents (CAs) have been an extensive research and development area. In the recent years, different inorganic-based nanoprobes comprising inorganic magnetic nanoparticles (MNPs) with an organic functional coating have been engineered to obtain a suitable contrast enhancement effect. For biomedical applications, the organic functional coating is critical to improve colloidal stability and biocompatibility. Simultaneously, it also provides a building block for generating a higher dimensional secondary structure. In this review, the combinatorial design approach by a self-assembling pre-formed hydrophobic inorganic MNPs core (from non-polar thermolysis synthesis) into various functional organic coatings (e.g. ligands, amphiphilic polymers and graphene oxide) to form water soluble nanocomposites will be discussed. The resultant magnetic ensembles were classified based on their dimensionality, namely, 0-D, 1-D, 2-D and 3-D structures. This classification provides further insight into their subsequent potential use as MRI CAs. Special attention will be dedicated towards the correlation between the spatial distribution and the associated MRI applications, which include (i) coating optimization-induced MR relaxivity enhancement, (ii) aggregation-induced MR relaxivity enhancement, (iii) off-resonance saturation imaging (ORS), (iv) magnetically-induced off-resonance imaging (ORI), (v) dual-modalities MR imaging and (vi) multifunctional nanoprobes.

Gd3N@C84(OH)x: A New Egg-Shaped Metallofullerene Magnetic Resonance Imaging Contrast Agent

Water-soluble derivatives of gadolinium-containing metallofullerenes have been considered to be excellent candidates for new magnetic resonance imaging (MRI) contrast agents because of their high relaxivity and characteristic encapsulation of the lanthanide ions (Gd(3+)), preventing their release into the bioenvironment. The trimetallic nitride template endohedral metallofullerenes (TNT EMFs) have further advantages of high stability, high relative yield, and encapsulation of three Gd(3+) ions per molecule as illustrated by the previously reported nearly spherical, Gd3N@I(h)-C80. In this study, we report the preparation and functionalization of a lower-symmetry EMF, Gd3N@C(s)-C84, with a pentalene (fused pentagons) motif and an egg-shaped structure. The Gd3N@C84 derivative exhibits a higher (1)H MR relaxivity compared to that of the Gd3N@C80 derivative synthesized the same way, at low (0.47 T), medium (1.4 T), and high (9.4 T) magnetic fields. The Gd3N@C(s)-C84 derivative exhibits a higher hydroxyl content and aggregate size, as confirmed by X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) experiments, which could be the main reasons for the higher relaxivity.

Microfluidic fabrication of 6-methoxyethylamino numonafide-eluting magnetic microspheres

Recently, 6-methoxyethylamino numonafide (MEAN) exhibited potent inhibition of hepatocellular carcinoma (HCC) cell growth and less systemic toxicity than amonafide. MEAN may serve as an ideal candidate for the treatment of HCC; however, liver-directed, selective infusion methods may be critical to maximize the MEAN dose delivered to the targeted tumors. This study describes the microfluidic fabrication of MEAN-eluting ultrasmall superparamagnetic iron oxide (USPIO) nanocluster-containing alginate microspheres (MEAN-magnetic microspheres) intended for selective transcatheter delivery to HCC. The resulting drug delivery platform was mono-disperse, microsphere sizes were readily controlled based on channel flow rates during synthesis procedures, and drug release rates from the microspheres could be readily controlled with the introduction of USPIO nanoclusters. The MR relaxivity properties of the microspheres suggest the feasibility of in vivo imaging after administration, and these microspheres exhibited potent therapeutic effects significantly inhibiting cell growth inducing apoptosis in hepatoma cells.

Multifunctional PEGylated nanoclusters for biomedical applications

A simple and versatile synthesis method to form water soluble multifunctional nanoclusters using polyethylene glycol (PEG) functionalized poly(maleic anhydride-alt-1-octadecene) amphiphilic brush copolymers (PMAO-g-PEG) was presented. Simply by tuning the core size and the initial nanocrystal concentration, manganese ferrite nanoparticles (MFNPs) were used to demonstrate the versatility of tuning the loading amount of the nanoclusters. The resultant nanoclusters were found to have a well-controlled spherical shape. When Zn-doped AgInS2 quantum dots (AIZS QDs) were loaded together with the MFNP nanocrystals, bi-functional nanoclusters with fluorescent and magnetic behaviors were obtained. Such bi-functional nanoclusters were also successfully demonstrated for cellular bio-imaging. Moreover, the presence of another type of nanocrystals together with MFNPs was found to have a negligible effect on the overall properties of the nanoclusters as demonstrated by the MR relaxivity test. From the time-dependent colloidal stability test, it was found that the presence of the PEG chain grafted onto PMAO was able to reduce protein adsorption onto the nanocluster surface. An in vitro study on NIH/3T3 demonstrated the biocompatibility of the nanoclusters. Such biocompatible and colloidally stable nanoclusters with an approximate size of 80-120 nm were suitable for both MRI and cell labeling applications.