T1 Contrast Agents Research Articles

Microemulsion-Confined Biomineralization of PEGylated Ultrasmall Fe3O4 Nanocrystals for T2-T1 Switchable MRI of Tumors.

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are a novel T1 contrast agent with good biocompatibility and switchable imaging signal that have not been widely applied for magnetic resonance imaging (MRI) because it is difficult to induce their relatively close ideal agglomeration. Here, by combining the microemulsion method with the biomineralization principle, a pH-responsive T2-T1 switchable MRI nanoprobe was constructed via the microemulsion-confined biomineralization of PEGylated USPIONs (PEG-USPIONs). The size of the formed CaCO3-coated PEG-USPION conjugates (PEG-USPIONs@CaCO3 nanoprobe) was uniform and controllable, and the preparation method was simple. The PEG-USPIONs inside the nanoconjugates agglomerate more tightly, and the T1-MRI signal of the nanoprobe is converted to the T2-MRI signal. When exposed to the acidic environment of the tumor tissue or internal organelles, the CaCO3-coating of the nanoprobes is dissolved, and free PEG-USPIONs are released, thus realizing the T1-weighted imaging of the tumors. The suitability of the PEG-USPIONs@CaCO3 nanoprobe for tumor MRI detection was successfully demonstrated using a mouse model bearing a subcutaneous 4T1 xenograft.

Effects of Electromagnets on Bovine Corneal Endothelial Cells Treated with Dendrimer Functionalized Magnetic Nanoparticles.

To improve bovine corneal endothelial cell (BCEC) migration, enhance cell energy, and facilitate symmetric cell distribution in corneal surfaces, an electromagnet device was fabricated. Twenty nanometer superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with fourth-generation dendrimer macromolecules were synthesized, and their size and structure were evaluated using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). The results confirmed the configuration of the dendrimer on the SPION surfaces. In vitro biocompatibility was assessed using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide assay. No significant toxicity was noted on BCECs within 24 h of incubation. In the cell migration assay, cells treated with dendrimer-coated SPIONs exhibited a relatively high wound healing rate under sample addition (1 μg/mL) under a magnetic field. Real-time PCR on BCECs treated with dendrimer-coated SPIONs revealed upregulation of specific genes, including AT1P1 and NCAM1, for BCECs-dendrimer-coated SPIONs under a magnetic field. The three-dimensional dispersion of BCECs containing dendrimer-coated SPIONs under a magnetic field was evaluated using COMSOL Multiphysics software. The results revealed the BCECs-SPION vortex pattern layers in the corneal surface corresponded to the electromagnet’s displacement from the ocular surface. Magnetic resonance imaging (MRI) indicated that dendrimer-coated SPIONs can be used as a T2 contrast agent.

Molecular Imaging Contrast Properties of Fe3O4‐Au Hybrid Nanoparticles for Dual‐Mode MR/CT Imaging Applications

AbstractThe development of noninvasive testing techniques in medicine by combining dual‐mode Magnetic Resonance (MR)/ Computed Tomography (CT) imaging techniques will help overcome the limitations of the separated methods, leading to more accurate diagnoses. This has implications in clinical research, but currently remains a major challenge in terms of the need for a corresponding multimodal signal contrast agent. In this study, we use small size, monodispersed Fe3O4 magnetic nanoparticles as the seeds to synthesize magneto‐plasmonic Fe3O4@Au hybrid nanoparticles (HNPs) with multiple functions with core‐shell structures. The influence of the ratios of HAuCl4 and oleyamine (OLA) precursors on the shape and size of the nanoparticles (NPs) was investigated. The HAuCl4/OLA ratio of 0.2/1 is the optimal condition. The obtained NPs has an average size of 21.2 nm with a uniform spherical shape, high monodispersity. After the surface functionalization with poly(acrylic acid) (PAA), the resulting Fe3O4@Au@PAA HNPs showed excellent dispersion in water, good biocompatibility, non‐toxicity against Hep‐G2 cancer cell line and Vero healthy cell line at high test concentration. The In‐vitro test data showed that the materials with Au shell enhance X‐ray decrease even at low concentrations compared to iodine‐based commercial substances while retaining the same effect as T2 contrast agent with high transverse relaxation rate r2 (125.2 mM−1s−1). The In‐vivo MRI images of rat liver tissue demonstrated that the hybrid nanoparticles showed the contrast increases 3 times under 1.5 T magnetic field after 30 minutes of drug administration. The computed tomography measurements showed the highest Hounsfield unit (HU) of 133.5 after the hybrid nanoparticle injected for 30 minutes. The in‐vivo efficacy of Fe3O4@Au@PAA magneto‐plasmonic hybrid nanoparticles was further evaluated in the cardiac and renal organs in a mouse test model to study drug kinetics. Generally, these Fe3O4@Au@PAA hybrid nanomaterials showed great promise as a candidate for multi‐modality molecular bio‐imaging.

Preparation and MRI performances of core-shell structural PEG salicylic acid-gadolinium composite nanoparticles

Gadolinium (III)-based T1 contrast agents have been widely used in clinical MRI. In this study, salicylic acid-gadolinium chelate was prepared via directly coordination reaction of gadolinium ion and salicylic acid. Then, three polyethylene glycols with different molecular weight were modified on the surface of salicylic acid-gadolinium by simple chemical coupling to construct three core-shell structural Gd based composites. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterization results show that the composite is a spherical particle with a diameter of about 100–200 nm. The longitudinal relaxation rate r1 of the Gal-PEG-2000 is 11.097 (mmol/L)−1/s, and the ratio of r2/r1 is as low as 2.53. The composite shows good liver and intestines MRI performances after being used in in vivo imaging, showing a good prospect of biological application.

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.

Preparation of Magnetic Resonance Nano Contrast Agent and Its Adoption in Diagnosis of Breast Cancer

This study aimed to explore the value of preoperative mammography in the differential diagnosis of benign and malignant tumors of nipple discharge. A biocompatible T1 contrast agent KMnF3 nanoparticle was first developed in the research, and then RGD-coupled KMnF3 nanoparticles were further synthesized as a highly sensitive tumor-targeted magnetic resonance imaging (MRI) contrast agent. While the nanoparticle was characterized physically, cytotoxicity test and MRI test in breast cancer mice were performed, and the excised tumors were subjected to immunostaining and tumor electron microscope section processing. At the same time, 60 patients with nipple discharge were screened to participate in the research, and the prepared MRI nano contrast agent was used for the differential diagnosis of breast benign/malignant tumors of nipple discharge. In the experiment, the synthetic nanoparticles were tested by Fourier transformed infrared (FTIR), which proved that the designed RGDtu/KMnF3 nanoparticles were successfully synthesized. The quantitative analysis of the synthesized nanoparticles showed that the relaxation efficiency reached 23.12 mM−1s−1, and there was no obvious toxicity. After staining, the microscope showed that the tumor was proliferating. After intravenous injection of low-dose RGDtu/KMnF3 contrast agent, nanoparticles were found in the tumor tissue. It was found that the synthesized nanoparticles enhanced the contrast of tumors with a volume of less than 50 mm3 by observing tumor slices. The imaging of the patient’s breast showed that the X-ray classification of galactography based on this contrast agent was statistically significant in distinguishing benign/malignant lesions of nipple discharge (X2 = 58.700, P < 0.01).

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

Exfoliation and in situ functionalization of MoS2 nanosheets for MRI-guided combined low-temperature photothermal therapy and chemotherapy

Traditional photothermal therapy (PTT) usually requires hyperthermia (greater than50 °C) to mediate effective tumor ablation, which could inevitably induce heating damage to the adjacent normal tissues. Therefore, to achieve effective tumor killing at relatively low temperature is crucial to improve the application of PTT. MoS2, as an attractive photothermal agents, have attracted much attention in biomedical applications. But the separation of exfoliation and functionalization of MoS2 nanosheets (NSs) partly complicates the preparation process of MoS2 NSs-based theranostic nanomaterials. Herein, we formulated a facile one-pot approach for the exfoliation and in situ functionalization of single-layer MoS2 nanosheets by using bovine serum albumin template gadolinium oxide (BSA-Gd2O3) nanoparticles as the exfoliating agent and magnetic resonance imaging (MRI) T1 contrast agent. On this basis, hyaluronic acid (HA) was further conjugated to target cancer cells with overexpression of CD44, and then gambogic acid (GA), a natural heat shock protein 90 inhibitor and antitumor drug was loaded, which could reduce the thermo-resistance of tumor cells and achieve effective PTT at a mild temperature (43–45 °C). In this research, both in vitro and in vivo experiments have confirmed that the GA/MoS2/BSA-Gd2O3-HA nanocomposite possesses good biocompatibility and is promising for the application in MRI-guided combined low-temperature PTT and chemotherapy.

Ultrasmall superparamagnetic iron oxide nanoparticles: A next generation contrast agent for magnetic resonance imaging.

As a research hotspot, the development of magnetic resonance imaging (MRI) contrast agents has attracted great attention over the past decades for improving the accuracy of diagnosis. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles with core diameter smaller than 5.0nm are expected to become a next generation of contrast agents owing to their excellent MRI performance, long blood circulation time upon proper surface modification, renal clearance capacity, and remarkable biosafety profile. On top of these merits, USPIO nanoparticles are used for developing not only T1 contrast agents, but also T2 /T1 switchable contrast agents via assembly/disassembly approaches. In recent years, as a new type of contrast agents, USPIO nanoparticles have shown considerable applications in the diagnosis of various diseases such as vascular pathological changes and inflammations apart from malignant tumors. In this review, we are focusing on the state-of-the-art developments and the latest applications of USPIO nanoparticles as MRI contrast agents to discuss their advantages and future prospects. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

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.

Target-Specific Magnetic Resonance Imaging of Human Prostate Adenocarcinoma Using NaDyF4-NaGdF4 Core-Shell Nanoparticles.

We illustrate the development of NaDyF4-NaGdF4 core-shell nanoparticles (NPs) for targeting prostate cancer cells using a preclinical 9.4 T magnetic resonance imaging (MRI) of live animals. The NPs composed of paramagnetic Dy3+ and Gd3+ (T2- and T1-contrast agents, respectively) demonstrate proton relaxivities of r1 = 20.2 mM-1 s-1 and r2 = 32.3 mM-1 s-1 at clinical 3 T and r1 = 9.4 mM-1 s-1 and r2 = 144.7 mM-1 s-1 at preclinical 9.4 T. The corresponding relaxivity values per NP are r1 = 19.4 × 105 mMNP-1 s-1 and r2 = 33.0 × 105 mMNP-1 s-1 at 3 T and r1 = 9.0 × 105 mMNP-1 s-1 and r2 = 147.0 × 105 mMNP-1 s-1 at 9.4 T. In vivo active targeting of human prostate tumors grown in nude mice revealed docking of anti-prostate-specific membrane antigen (PSMA) antibody-tagged NPs at tumor sites post-24 h of their intravenous injection. On the other hand, in vivo passive targeting showed preferential accumulation of NPs at tumor sites only within 2 h of their injection, ascribed to the enhanced permeation and retention effect of the tumor. A biodistribution study employing the harvested organs of mice, post-24 h injection of NPs, quantified active targeting as nearly twice as efficient as passive targeting. These outcomes provide potential opportunities for noninvasive diagnosis using NaDyF4-NaGdF4 core-shell NPs for target-specific MRI.

Target-switchable Gd(III)-DOTA/protein cage nanoparticle conjugates with multiple targeting affibody molecules as target selective T1 contrast agents for high-field MRI

Magnetic resonance imaging (MRI) is a non-invasive in vivo imaging tool, providing high enough spatial resolution to obtain both the anatomical and the physiological information of patients. However, MRI generally suffers from relatively low sensitivity often requiring the aid of contrast agents (CA) to enhance the contrast of vessels and/or the tissues of interest from the background. The targeted delivery of diagnostic probes to the specific lesion is a powerful approach for early diagnosis and signal enhancement leading to the effective treatment of various diseases. Here, we established targeting ligand switchable nanoplatforms using lumazine synthase protein cage nanoparticles derived from Aquifex aeolicus (AaLS) by genetically introducing the SpyTag peptide (ST) to the C-terminus of the AaLS subunits to form an ST-displaying AaLS (AaLS-ST). Conversely, multiple targeting ligands were constructed by genetically fusing SpyCatcher protein (SC) to either HER2 or EGFR targeting affibody molecules (SC-HER2Afb or SC-EGFRAfb). Gd(III)-DOTA complexes were chemically attached to the AaLS-ST and the external surface of the Gd(III)-DOTA conjugated AaLS-ST (Gd(III)-DOTA-AaLS-ST) were successfully decorated with either the HER2Afb or the EGFRAfb. The resulting Gd(III)-DOTA-AaLS/HER2Afb and Gd(III)-DOTA-AaLS/EGFR2Afb exhibited high r1 relaxivity values of 57 and 25 mM−1 s−1 at 1.4 and 7 T, respectively, which were 10-fold or higher than those of the clinically used Dotarem. Their target-selective contrast enhancements were confirmed with in vitro cell-based MRI scans and the in vivo MR imaging of tumor-bearing mouse models at 7 T. A target-switchable AaLS-based nanoplatform that was developed in this study might serve as a promising T1 CA developing platform at a high magnetic field to detect various tumor sites in a target-specific manner in future clinical applications.

PVP Surface-protected silica coated iron oxide nanoparticles for MR imaging application

This paper proposed an engineered mesoporous silica-coated Fe3O4 nanoparticle, PVPMSFe, prepared by a sol-gel/surface-protected etching mechanism as an MRI T2 contrast agent. To this end, the structural characterization of the nanocomposite was performed by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET) method, VSM, thermogravimetric analysis (TGA), TEM, FESEM, and energy-dispersive X-ray scanning electron microscopy (EDS). The findings show that the synthesized nanocomposite has a mesoporous structure with an average particle size of 11.8 nm and excellent magnetization properties. The biocompatibility of PVPMSFe was investigated by MTT assay and hemolysis assay of red blood cells and the results indicate that PVPMSFe has favorable biocompatibility. Besides, the effect of PVPMSFe was assessed with MRI relaxivity measurement (T2 signal). Regarding the in vitro MRI relaxivity measurements outputs (r2 =144.4), PVPMSFe can attenuate the T2 signal of MRI, perfectly which makes it an efficient T2 contrast agent.

Magneto-Erythrocyte Membrane Vesicles’ Superior T2 MRI Contrast Agents to Magneto-Liposomes

Despite their high potential, most of the clinically approved iron oxide (IO)-based contrast agents for magnetic resonance imaging (MRI) have been withdrawn from the market either due to safety issues or lack of sales. To address this challenge, erythrocyte membranes have been used to prepare IO-based T2 contrast agents with superior MRI properties and higher safety margin. A simple formulation procedure has been proposed, and the nanostructures’ morphology and physicochemical properties have been evaluated. We compared their performance in terms of contrast ability in MRI to the more clinically established magneto-liposomes and non-encapsulated nanoparticles (NPs). The encapsulation of 5-nm iron oxide nanoparticles (IO NPs) in the liposomes and erythrocyte membrane vesicles (EMVs) led to a significant improvement in their r2 relaxivity. r2 values increased to r2 = 188 ± 2 mM−1s−1 for magneto-liposomes and r2 = 269 ± 3 mM−1s−1 for magneto-erythrocyte membranes, compared to “free” IO NPs with (r2 = 12 ± 1 mM−1 s−1), measured at a 9.4 T MRI scanner. The superiority of magneto-erythrocyte membranes in terms of MRI contrast efficacy is clearly shown on T2-weighted MR images. Our study revealed the hemocompatibility of the developed contrast agents in the MRI-relevant concentration range.

An Activatable T1-Weighted MR Contrast Agent: A Noninvasive Tool for Tracking the Vicinal Thiol Motif of Thioredoxin in Live Cells.

We have synthesized new magnetic resonance imaging (MRI) T1 contrast agents (CA1 and CA2) that permit the activatable recognition of the cellular vicinal thiol motifs of the protein thioredoxin. The contrast agents showed MR relaxivities typical of gadolinium complexes with a single water molecule coordinated to a Gd3+ center (i.e., ~4.54 mM−1s−1) for both CA1 and CA2 at 60 MHz. The contrast agent CA1 showed a ~140% relaxivity enhancement in the presence of thioredoxin, a finding attributed to a reduction in the flexibility of the molecule after binding to thioredoxin. Support for this rationale, as opposed to one based on preferential binding, came from 1H-15N-HSQC NMR spectral studies; these revealed that the binding affinities toward thioredoxin were almost the same for both CA1 and CA2. In the case of CA1, T1-weighted phantom images of cancer cells (MCF-7, A549) could be generated based on the expression of thioredoxin. We further confirmed thioredoxin expression-dependent changes in the T1-weighted contrast via knockdown of the expression of the thioredoxin using siRNA-transfected MCF-7 cells. The nontoxic nature of CA1, coupled with its relaxivity features, leads us to suggest that it constitutes a first-in-class MRI T1 contrast agent that allows for the facile and noninvasive monitoring of vicinal thiol protein motif expression in live cells.

Gd3+ Doped CoFe2O4 Nanoparticles for Targeted Drug Delivery and Magnetic Resonance Imaging

Nanoparticles of CoGdxFe2 − xO4 (x = 0%, 25%, 50%) synthesized via sol–gel auto combustion technique and encapsulated within a polymer (Eudragit E100) shell containing curcumin by single emulsion solvent evaporation technique were formulated in this study. Testing of synthesized nanoparticles was carried out by using different characterization techniques, to investigate composition, crystallinity, size, morphology, surface charge, functional groups and magnetic properties of the samples. The increased hydrophilicity resulted in sustained drug release of 90.6% and 95% for E1(CoGd0.25Fe1.75O4) and E2(CoGd0.50Fe1.5O4), respectively, over a time span of 24 h. The relaxivities of the best-chosen samples were measured by using a 3T magnetic resonance imaging (MRI) machine, and a high r2/r1 ratio of 43.64 and 23.34 for composition E1(CoGd0.25Fe1.75O4) and E2(CoGd0.50Fe1.5O4) suggests their ability to work as a better T2 contrast agent. Thus, these novel synthesized nanostructures cannot only enable MRI diagnosis but also targeted drug delivery.

Preparation of Graphene Oxide/Fe3O4 Nanocomposite as a Potential Magnetic Nanocarrier and MRI Contrast Agent

AbstractIn this paper, graphene oxide/ magnetite (GO/Fe3O4) nanocomposite was synthesized as a carrier and MRI contrast agent. X‐ray diffraction (XRD) indicated that the crystalline structure of Fe3O4 nanoparticles and Furrier transform infrared spectroscopy (FT‐IR) provided evidence for the presence of Fe3O4 and GO in the nanocomposite. The surface morphology of the nanocomposite was studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The magnetic properties of the synthesized nanocomposite was studied by a vibrating sample magnetometer (VSM). The drug loading and encapsulation efficiency of the curcumin were 22 and 96 %, respectively. The comparison between drug release from GO/Fe3O4 in neutral and acidic pH was shown high release in neutral conditions. MTT results demonstrated that the GO/Fe3O4 nanocomposite illustrates considerable toxicity due to which cell viability decreased to lower than 50 % at 140 μg ml−1 concentration. The results showed that curcumin and curcumin loaded nanocomposite has a similar power of antioxidant activities. GO/Fe3O4 nanocomposite is a good magnetic resonance T2 contrast agent under the T2‐imaging sequences. The novelty of this study is the application of water‐dispersed GO/Fe3O4 with pH‐dependent release properties for designing a new colon drug delivery.

Glutathione-Responsive Magnetic Nanoparticles for Highly Sensitive Diagnosis of Liver Metastases.

Liver metastasis (LM) occurs in various cancers, and its early and accurate diagnosis is of great importance. However, the detection of small LMs is still a great challenge because of the subtle differences between normal liver tissue and small metastases. Herein, we prepare glutathione (GSH)-responsive hyaluronic acid-coated iron oxide nanoparticles (HIONPs) for highly sensitive diagnosis of LMs through a facile one-pot method. HIONPs greatly enhance the signal of MRI in tumor metastases as T1 contrast agent (CA), whereas they substantially decrease the signal of liver as T2 CA as they aggregate into clusters upon the high GSH in liver. Consequently, MRI contrasted by HIONPs clearly distinguishes metastatic tumors (bright) from surrounding liver tissues (dark). HIONPs with superior LM contrasting capability and facile synthesis are very promising for clinical translation and indicate a new strategy to develop an ultrasensitive MRI CA for LM diagnosis that exploits high GSH level in the liver.

A Novel Mesoporous Superparamagnetic Hybrid Silica/Hydroxyapatite Nanocomposite as MRI Contrast Agent

AbstractThis paper introduces a novel magnetic hybrid silica/hydroxyapatite nanocomposite with a mesoporous structure, MSFeHA. The usefulness of the nanocomposite as an MRI T2 contrast agent was studied. The structure and morphology of the nanocomposite were characterized by FT‐IR, XRD, N2 adsorption‐desorption isotherms, VSM, TEM, SEM, and EDS‐MAP. Then, the biocompatibility of the synthesized nanocomposite was studied by Brine shrimp Artemia lethality assay, red blood cell hemolysis assay, and MTT assay on MCF‐7 breast cancer cell line and HFF‐2 normal cell line. ICP‐OES results indicate that the highest bioaccumulation of MSFeHA nanocomposite has occurred within the liver and, between 4 to 24 hours after administration of MSFeHA. The amount of bioaccumulation within the studied organs decreased over time, which suggests that the nanocomposite biodegradation and excretion process became started. Furthermore, in vitro MRI studies reveal that MSFeHA nanocomposite has the potential to be an MRI T2 contrast agent (r2=106.6 ms).

Colloidally Stable Monodisperse Fe Nanoparticles as T2 Contrast Agents for High-Field Clinical and Preclinical Magnetic Resonance Imaging

Iron nanoparticles (Fe NPs) produce negative contrast in magnetic resonance imaging (MRI) by shortening the transverse relaxation time (T2) of water protons at tissue sites. The high sensitivity of Fe toward oxidation under ambient conditions has challenged and impeded the development of stable Fe NPs for bioapplications compared to iron oxide nanoparticles (IONPs). This article demonstrates the synthesis of three batches of fairly monodisperse (size dispersion, <10%), colloidal Fe NPs with inorganic core diameters of 15.2, 12.0, and 8.8 nm. The 15.2 nm Fe NPs show high stability against oxidation, beyond 5 months, when dispersed in chloroform and deionized water. Upon dispersion in deionized water, these NPs gradually develop an amorphous iron oxide shell. On the contrary, upon transfer into water, the smaller Fe NPs oxidize to amorphous iron oxide eventually. The 15.2 nm Fe NPs exhibit much stronger shortening of the T2 relaxation time compared to the 12.0 and 8.8 nm Fe NPs at both high-field clinical 3 T and preclinical 9.4 T. The transverse relaxivity (r2) values of the 15.2 nm Fe NPs, based on per Fe ion concentration, were determined to be 167.9 mM–1 s–1 at 3 T and 236.4 mM–1 s–1 (higher than similarly sized IONPs) at 9.4 T. The respective r2/r1 ratios of 280 and 788 are high for a T2 contrast agent, although comprehensive MRI data for Fe NPs are not available in the literature for direct comparison. Fe NPs are promising MRI contrast agents for medical imaging.