T1 Magnetic Resonance Imaging Contrast Research Articles

In Vivo Positive Magnetic Resonance Imaging Applications of Poly(methyl vinyl ether-alt-maleic acid)-coated Ultra-small Paramagnetic Gadolinium Oxide Nanoparticles.

The study of ultra-small paramagnetic gadolinium oxide (Gd2O3) nanoparticles (NPs) as in vivo positive (T1) magnetic resonance imaging (MRI) contrast agents is one of the most attractive fields in nanomedicine. The performance of the Gd2O3 NP imaging agents depends on the surface-coating materials. In this study, poly(methyl vinyl ether-alt-maleic acid) (PMVEMA) was used as a surface-coating polymer. The PMVEMA-coated paramagnetic ultra-small Gd2O3 NPs with an average particle diameter of 1.9 nm were synthesized using the one-pot polyol method. They exhibited excellent colloidal stability in water and good biocompatibility. They also showed a very high longitudinal water proton spin relaxivity (r1) value of 36.2 s−1mM−1 (r2/r1 = 2.0; r2 = transverse water proton spin relaxivity) under a 3.0 tesla MR field which is approximately 10 times higher than the r1 values of commercial molecular contrast agents. High positive contrast enhancements were observed in in vivo T1 MR images after intravenous administration of the NP solution sample, demonstrating its potential as a T1 MRI contrast agent.

Surface Effects of Ultrasmall Iron Oxide Nanoparticles on Cellular Uptake, Proliferation, and Multipotency of Neural Stem Cells

Ultrasmall iron oxide nanoparticles (USIONPs) have been recently developed as labeling probes for T2 magnetic resonance imaging contrast agents. However, their use in stem cell tracking has been limited, especially as T1 contrast agents. In this study, we studied the effects of USIONP surface coatings on proliferation, cellular uptake, and multipontency of established and primary neural stem cells (NSCs). USIONPs were functionalized with gluconic acid (GA), tannic acid (TA), and hyaluronic acid (HA) to label the NSCs. All functionalized USIONPs were characterized as T1 contrast agents via relaxivity measurements. Direct functionalization with TA and HA-coating promoted NSC proliferation and enhanced cellular uptake in a dose-dependent manner than those with GA. Furthermore, HA-coating showed enhanced cell proliferation and cellular uptake in primary NSCs depending on the HA molecular weight. Stem cell characteristics were well-maintained, verified by neurosphere formation and gene expression of stemness a...

Mesoporous Silica Hybridized With Gadolinium(III) Nanoplatform for Targeted Magnetic Imaging-Guided Photothermal Breast Cancer Therapy.

Achieving drug target accumulation in antitumor tissue, simultaneous diagnostic imaging, and optimal release behavior with treatment needs a best chemotherapy procedure involving receptive switch of drug delivery. Constructed on mesoporous silica nanoparticles, which are crossed with multiscale charming nanoparticles for magnetic resonance imaging (MRI)-aided and alternate magnetic field (AMF) response chemotherapy for breast cancer, we report in this work the assembly of a new theranostics drug conveyance process. Hydrothermal processes (gadolinium(III) oxide nanoparticles [Gd-NPs]) and heat decomposition process (radical size uFe-NPs) were used to prepare superparamagnetic Gd-NPs with multiscale sizes. Gadolinium(III) oxide nanoparticles act as an AMF-responsive heat mediator, while ultra-Fe nanoparticles (uFe-NPs) act as an MRI T2 contrast mediator. Nanoparticles of the mesoporous silica with radially oriented mesochannels were further grown in situ on the surfaces of the Gd-NPs, and the uFe-NPs anticancer drug doxorubicin can be easily incorporated in the mesochannels. To provide better targeting capabilities for the as-synthesized biotin-loaded nanohybrids, the particle surfaces are updated with biotin (Bt). This optimized drug conveyance method based on nanocomposites of SiO2 demonstrated great efficiency of medication charging and receptive properties of AMF stimulus release. However, tests of MRI in vitro showed an outstanding contrast effect in MRI with a high stimulation quality (299 mM−1 s−1). In contrast, the study of in vitro cytotoxicity assessment revealed that an MRI-directed stimulus-mediated theranostics tool can be used as a drug conveyance device to efficiently treat breast cancer.

A Dual-Modality MR/PA Imaging Contrast Agent Based on Ultrasmall Biopolymer Nanoparticles for Orthotopic Hepatocellular Carcinoma Imaging.

BackgroundHepatocellular carcinoma (HCC) is the second leading cause of cancer death and early stage diagnosis can greatly increase the survival rate of patient. However, the accurate detection of HCC remains an urgent challenge in medical diagnosis. The combination of magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) are conducive for accurate locating of cancerous tissue. Therefore, it is necessary to explore a more facile and biosafe dual-modal contrast agent for orthotopic HCC detection.MethodsIn this study, a promising contrast agent had been identified based on gadolinium chelated melanin nanoparticles and evaluated its usage as a dual-modal T1 MRI and PAI contrast agent for orthotopic HCC detection.ResultsThe gadolinium-based melanin nanoparticles presented ultrasmall size, high chelation stability and negligible cytotoxicity estimated by CCK-8 assay. Moreover, the nanoparticle exhibited higher r1 relaxivity (45.762 mM−1 s−1) than clinically approved Gadodiamide (4.975 mM−1 s−1) at 1.5 T MR scanning. A linear regression analysis confirmed that the nanoparticles were ideal candidates for PAI in vitro. After the nanoparticles were injected into vein in mice with orthotopic HCC, a dramatic increase in signal of the liver was observed at 0.5 hr by MRI and PAI, while the tumor exerted remarkable signal enhancement at 7 hrs, showing excellent detection sensitivity. In addition, the nanoparticles exhibited excellent biocompatibility and they can be excreted through both hepatobiliary and renal pathways after diagnosis.ConclusionThese results indicate that the ultrasmall gadolinium chelated melanin nanoparticles is a promising candidate as a dual-modal MRI/PAI contrast agent for the detection of orthotopic HCC.

D‐Glucuronic Acid‐Coated Ultrasmall Paramagnetic Ln2O3 (Ln = Tb, Dy, and Ho) Nanoparticles: Magnetic Properties, Water Proton Relaxivities, and Fluorescence Properties

Many of the lanthanide‐based nanoparticles are valuable in magnetic resonance imaging (MRI) because they have excellent magnetic properties that make them suitable for MRI contrast agents, while some of them have additional optical properties and thus can serve as fluorescence imaging (FI) agents as well. Herein, we synthesized d‐glucuronic acid‐coated ultrasmall Ln2O3 (Ln = Tb, Dy, and Ho) nanoparticles with average diameters of ∼ 2 nm. All the nanoparticles showed unsaturated but appreciable magnetization of ∼ 4 emu/g at an applied field of 1.8 T at room temperature, and consequently, high transverse water proton relaxivities (r2) of ∼ 7 s–1 mm–1 at 1.5 T, ∼ 35 s–1 mm–1 at 3.0 T, and ∼ 55 s–1 mm–1 at 9.4 T with negligible longitudinal water proton relaxivities (r1), thus being eligible for use as T2 MRI contrast agents at high MR fields. In addition, d‐glucuronic acid‐coated ultrasmall Tb2O3 nanoparticles exhibited fluorescence in the green region, useful for dual‐modal imaging.

Small-Sized MOF-Constructed Multifunctional Diagnosis and Therapy Platform for Tumor.

In this article, a type of small-sized metal organic framework (MOF), MIL-101(Fe), as an intelligent delivery system was fabricated to load chemotherapy drug dihydroartemisinin (DHA) and photosensitizer methylene blue (MB). In addition, the Fe ions releasedfrom the MOFs in the tumor environment not only enhanced the curative effect of DHA but also catalyzed H2O2 to release O2, which further improved the photodynamic therapeutic effect of the nanocomposites. The nanocomposites can serve as a T2 magnetic resonance imaging contrast agent at the same time. The polylactic acid (PLA) and polyethylene glycol (PEG) were used to modify the surface of MOFs-MB-DHA to acquire the excellent controllable release of drugs and good biocompatibility to decrease the side effects for normal cells. All the results show remarkably increase of the therapeutic efficiency by synergistic chemo-photodynamic therapy. Thus, a smart multifunctional drug delivery system for diagnosis and therapy based on MOFs-MB-DHA@PLA@PEG was constructed for not only real-time imaging but also chemotherapy and photodynamic synergetic therapy to kill the tumor selectively, showing great potential for conquering the existing barrier in chemo-photodynamic synergetic therapy.

Macromolecules with Different Charges, Lengths, and Coordination Groups for the Coprecipitation Synthesis of Magnetic Iron Oxide Nanoparticles as T1 MRI Contrast Agents.

Considerable efforts have been focused on the exploitation of macromolecule ligands for synthesis of magnetic Fe3O4 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents, but studies that concern macromolecule ligands with different charges and coordination groups are still limited. Herein, we used poly(acrylic acid) (PAA), poly(allylamine hydrochloride) (PAH), and polyvinyl alcohol (PVA), which possess negative, positive and neutral charges with carboxylic acid, amino and hydroxyl groups respectively, as templates and stabilizers to fabricate Fe3O4 nanoparticles through coprecipitation reaction. The obtained Fe3O4-PAA, Fe3O4-PAH, and Fe3O4-PVA nanoparticles showed T1 contrast performance with r1 relaxivities of 23.4, 60.3, and 30.6 mM s−1 at 0.5 T (25 °C), and a r2/r1 ratio of 2.62, 3.82, and 7.26, respectively. The cell viability assay revealed that Fe3O4-PAA and Fe3O4-PVA exhibited good biocompatibility, while Fe3O4-PAH displayed high cytotoxicity. In vivo T1-weighted (1 T) mice showed that both Fe3O4-PAA and Fe3O4-PVA were able to display remarkably brighten the contrast enhancement for the mice tumor and kidney sites, but Fe3O4-PAA had better contrast performance. This work highlights that the macromolecule ligands play an important role in the biocompatibility and T1 contrast performance of magnetic Fe3O4 nanoparticles.

Role of Surface Chemistry in Mediating the Uptake of Ultrasmall Iron Oxide Nanoparticles by Cancer Cells.

Ultrasmall iron oxide nanoparticles (USIONPs) (<4 nm) have recently attracted significant attention because of their potential as positive T1 magnetic resonance imaging (MRI) contrast agent contrary to larger superparamagnetic iron oxide nanoparticles (>6 nm) which act as negative T2 MRI contrast agents. However, studies on the cellular uptake behavior of these nanoparticles are very limited compared to their counterpart, larger-sized superparamagnetic iron oxide nanoparticles. In particular, the effects of specific nanoparticle parameters on the cellular uptake behavior of USIONPs by various cancer cells are not available. Here, we specifically investigated the role of USIONPs' surface functionalities [tannic acid (TA) and quinic acid (QA)] in mediating cellular uptake behavior of cancer cells pertaining to primary (U87 cells) and metastatic (MDA-MB-231Br cells) brain malignancies. Here, we chose TA and QA as representative capping molecules, wherein TA coating provides a general negatively charged nontargeting surface while QA provides a tumor-targeting surface as QA and its derivatives are known to interact with selectin receptors expressed on tumor cells and tumor endothelium. We observed differential cellular uptake in the case of TA- and QA-coated USIONPs by cancer cells. Both the cell types showed significantly higher cellular uptake of QA-coated USIONPs compared to TA-coated USIONPs at 4, 24, and 72 h. Blocking studies indicated that P-selectin cell surface receptors, in part, mediated the cellular uptake of QA-coated USIONPs. Given that P-selectin is overexpressed in cancer cells, tumor microenvironment, and at the metastatic niche, QA-coated USIONPs hold potential to be utilized as a platform for tumor-targeted drug delivery and in imaging and detection of primary and metastatic tumors.

Bifunctional Pyrrolidin-2-one Terminated Manganese Oxide Nanoparticles for Combined Magnetic Resonance and Fluorescence Imaging.

Multimodal probes are an asset for simplified, improved medical imaging. In particular, fluorescence and magnetic resonance imaging (MRI) are sought-after combined capabilities. Here, we show that pyrrolidin-2-one-capped manganese oxide nanoparticles (MnOpyrr NPs) combine MRI with fluorescence microscopy to function as efficient bifunctional bio-nanoprobes. We employ a one-pot synthesis for ca. 10 nm MnO NPs, wherein manganese(II) 2,4-pentadionate is thermally decomposed using pyrrolidin-2-one as a solvent and capping ligand. The MnOpyrr NPs are soluble in water without any further postsynthetic modifications. The r1 relaxivity and r2 /r1 ratio indicate that these NPs are potential T1 MRI contrast agents at clinical (3 T) and ultrahigh (9.4 T) magnetic fields. Serendipitously, the as-prepared NPs are photoluminescent. The unexpected luminescence is ascribed to the modification of the pyrrolidin-2-one during the thermal treatment. MnOpyrr NPs are successfully used to enable fluorescence microscopy of HeLa cells, demonstrating bifunctional imaging capabilities. A low cytotoxic response in two distinct cell types (HeLa, HepG2) supports the suitability of MnOpyrr NPs for biological imaging applications.

Novel Hybrid Dextran-Gadolinium Nanoparticles as High-relaxivity T1 Magnetic Resonance Imaging Contrast Agent for Mapping the Sentinel Lymph Node.

To assess the applicability of a novel hybrid dextran-gadolinium nanoparticles (NPs) as high-relaxivity T1 magnetic resonance imaging (MRI) contrast agent for mapping the sentinel lymph node (SLN). Dextran-bis-acrylamide-polyacrylic acid (Dex-MBA-PAA) NPs were synthesized through a self-assembly assisted approach and complexed with multiple chelated gadolinium (Gd) (III) ions. After their characterization was validated, they were used to mapping SLNs by MRI in Wistar rats, and their biosafety was evaluated. Dextran-MBA-polyacrylic acid-Gd NPs have suitable particle size and much higher longitudinal relaxivity (r1) than that of commonly used clinical MRI contrast agents (eg, gadopentetic acid dimeglumine salt injection). The in vivo T1-weighted MRI results revealed their effectiveness at mapping SLNs. And their biological safety was also verified. Dextran-MBA-polyacrylic acid-Gd NPs were synthesized and validated by in vitro and in vivo experiments for their ability to visualize SLNs by MRI with accurate positioning and excellent biosafety, and they have great potential for clinical SLN mapping.

Targeted T1 Magnetic Resonance Imaging Contrast Enhancement with Extraordinarily Small CoFe2O4 Nanoparticles.

Extraordinarily small (2.4 nm) cobalt ferrite nanoparticles (ESCIoNs) were synthesized by a one-pot thermal decomposition approach to study their potential as magnetic resonance imaging (MRI) contrast agents. Fine size control was achieved using oleylamine alone, and annular dark-field scanning transmission electron microscopy revealed highly crystalline cubic spinel particles with atomic resolution. Ligand exchange with dimercaptosuccinic acid rendered the particles stable in physiological conditions with a hydrodynamic diameter of 12 nm. The particles displayed superparamagnetic properties and a low r2/r1 ratio suitable for a T1 contrast agent. The particles were functionalized with bile acid, which improved biocompatibility by significant reduction of reactive oxygen species generation and is a first step toward liver-targeted T1 MRI. Our study demonstrates the potential of ESCIoNs as T1 MRI contrast agents.

Facile solvothermal synthesis and functionalization of polyethylene glycol-coated paramagnetic Gd2(CO3)3 particles and corresponding Gd2O3 nanoparticles for use as MRI contrast agents

Abstract Paramagnetic particles and nanoparticles have been widely used in bioimaging and biomedical applications. In this paper, functionalized gadolinium carbonate (Gd2(CO3)3) particles with polyethylene glycol (PEG) for use as an MRI contrast agent were produced. These PEGylated particles were also used as a single precursor for synthesizing Gd2O3 nanoparticles by a novel calcination pathway. The morphological, chemical, and structural properties of both the PEGylated Gd2(CO3)3 particles and Gd2O3 nanoparticles were examined using a scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), and energy dispersive X-ray spectroscopy (EDS) techniques. After the calcination process at a temperature of 800 °C, the amorphous, rhombus flakes of PEGylated Gd2(CO3)3 were converted into crystalline nanospherical Gd2O3 particles with an average diameter of 80 nm. The hydrophilic polymer coating of PEG successfully attached to the Gd2(CO3)3 particles which resulted in high dispersibility and stability in a water based solution. The magnetic properties were investigated using a vibrating sample magnetometer (VSM), which showed that the PEGylated Gd2(CO3)3 and Gd2O3 exhibit paramagnetic character. Furthermore, in vitro magnetic resonance imaging (MRI) demonstrated that PEGylated Gd2(CO3)3 particles show a promising T1 weighted effect and could potentially serve as a T1 MRI contrast agent.

Dual T1/ T2 Nanoscale Coordination Polymers as Novel Contrast Agents for MRI: A Preclinical Study for Brain Tumor.

In the last years, extensive attention has been paid on designing and developing functional imaging contrast agents for providing accurate noninvasive evaluation of pathology in vivo. However, the issue of false-positives or ambiguous imaging and the lack of a robust strategy for simultaneous dual-mode imaging remain to be fully addressed. One effective strategy for improving it is to rationally design magnetic resonance imaging (MRI) contrast agents (CAs) with intrinsic T1/ T2 dual-mode imaging features. In this work, the development and characterization of one-pot synthesized nanostructured coordination polymers (NCPs) which exhibit dual mode T1/ T2 MRI contrast behavior is described. The resulting material comprises the combination of different paramagnetic ions (Fe3+, Gd3+, Mn2+) with selected organic ligands able to induce the polymerization process and nanostructure stabilization. Among them, the Fe-based NCPs showed the best features in terms of colloidal stability, low toxicity, and dual T1/ T2 MRI contrast performance overcoming the main drawbacks of reported CAs. The dual-mode CA capability was evaluated by different means: in vitro phantoms, ex vivo and in vivo MRI, using a preclinical model of murine glioblastoma. Interestingly, the in vivo MRI of Fe-NCPs show T1 and T2 high contrast potential, allowing simultaneous recording of positive and negative contrast images in a very short period of time while being safer for the mouse. Moreover, the biodistribution assays reveals the persistence of the nanoparticles in the tumor and subsequent gradual clearance denoting their biodegradability. After a comparative study with commercial CAs, the results suggest these nanoplatforms as promising candidates for the development of dual-mode MRI CAs with clear advantages.

Artificially controlled degradable nanoparticles for contrast switch MRI and programmed cancer therapy.

BackgroundUtilizing the permeability enhancement and irreversible biomolecule denaturation caused by hyperthermia, photothermal-chemo synergistic therapy has shown great potential in clinical cancer treatment.PurposeThe objective of this study was to provide a novel controlled drug release method to improve the efficiency of photothermal-chemo synergistic therapy.Patients and methodsHCT116 tumor-bearing mice were selected as modal for the study of cancer theranostics efficiency. The T2 to T1 magnetic resonance imaging contrast switch was studied in vivo. Analyses of the tumor growth of mice were carried out to evaluate the tumor therapy efficiency.ResultsWe developed novel artificially controlled degradable Co3O4 nanoparticles and explored their potential in drug delivery/release. In the presence of ascorbic acid (AA), the designed nanomaterials can be degraded via a redox process and hence release the loaded drugs. Importantly, the AA, in the lack of l-gulonolactone oxidase, cannot be synthesized in the body of typical mammal including human, which suggested that the degradation process can be controlled artificially. Moreover, the obtained nanoparticles have outstanding photothermal conversion efficiency and their degradation can also result in an magnetic resonance imaging contrast enhancement switch from T2 to T1, which benefits the cancer theranostics.ConclusionOur results illustrated that the artificially controlled degradable nanoparticles can serve as an alternative candidate for controllable drug release as well as a platform for highly efficient photothermal-chemo synergistic cancer theranostics.

Tolerogenic Iron Oxide Nanoparticles in Type 1 Diabetes: Biodistribution and Pharmacokinetics Studies in Nonobese Diabetic Mice.

Nanoparticle (NP) administration is among the most attractive approaches to exploit the synergy of different copackaged molecules for the same target. In this work, iron oxide NPs are surface-engineered for the copackaging of the autoantigen proinsulin, a major target of adaptive immunity in type 1 diabetes (T1D), and 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methylester (ITE), a small drug conditioning a tolerogenic environment. Magnetic resonance imaging (MRI) combined with magnetic quantification are used to investigate NP biokinetics in nonobese diabetic (NOD) mice and control mice in different organs. Different NP biodistribution, with in particular enhanced kidney elimination and a stronger accumulation in the pancreas for prediabetic NOD mice, is observed. This is related to preferential NP accumulation in the pancreatic inflammatory zone and to enhancement of renal elimination by diabetic nephropathy. For both mouse strains, an MRI T2 contrast enhancement at 72 h in the liver, pancreas, and kidneys, and indicating recirculating NPs, is also found. This unexpected result is confirmed by magnetic quantification at different time points as well as by histological evaluation. Besides, such NPs are potential MRI contrast agents for early diagnosis of T1D.

Routes to Potentially Safer T1 Magnetic Resonance Imaging Contrast in a Compact Plasmonic Nanoparticle with Enhanced Fluorescence

Engineering a compact, near-infrared plasmonic nanostructure with integrated image-enhancing agents for combined imaging and therapy is an important nanomedical challenge. Recently, we showed that Au@SiO2@Au nanomatryoshkas (NM) are a highly promising nanostructure for hosting either T1 MRI or fluorescent contrast agents with a photothermal therapeutic response in a compact geometry. Here, we show that a near-infrared-resonant NM can provide simultaneous contrast enhancement for both T1 magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI) by encapsulating both types of contrast agents in the internal silica layer between the Au core and shell. We also show that this method of T1 enhancement is even more effective for Fe(III), a potentially safer contrast agent compared to Gd(III). Fe-NM-based contrast agents are found to have relaxivities 2× greater than those found in the widely used gadolinium chelate, Gd(III) DOTA, providing a practical alternative that would eliminate Gd(III) patient exposure entirely. This dual-modality nanostructure can enable not only tissue visualization with MRI but also fluorescence-based nanoparticle tracking for quantifying nanoparticle distributions in vivo, in addition to a near-infrared photothermal therapeutic response.

Reduced Magnetic Coupling in Ultrasmall Iron Oxide T1 MRI Contrast Agents

Contrast agents for magnetic resonance imaging (MRI) are essential for evidential visualization of soft tissues pathologies. Contrast-enhanced MRI can be carried out with T1- and T2-weighted sequences that require as contrast agents paramagnetic and superparamagnetic materials, respectively. The T1-weighted imaging is frequently preferred over T2-, as it induces a bright contrast for sharper image analysis and allows more rapid image acquisition. Commonly used and FDA-approved T1 contrast agents, however, were shown to be associated with nephrogenic systematic fibrosis due to Gd3+ release from the injected complexes. Here, ultrasmall iron oxide nanocrystals are produced by scalable flame aerosol technology and investigated as T1 MRI contrast agents by focusing on structure-function relationships and cytocompatibility. The optimized nanocrystals are shown to be a promising cytocompatible alternative to commercial Gd-complexes as they attain comparable relaxivities with no apparent cytotoxicity at clinically relevant concentrations tested in vitro against four different cell types (PC3, HepG2, THP-1, and red blood cells). By using SiO2 as a spacing material, the contrast enhancement could be finely tuned by decreasing the effective magnetic size of iron oxide resulting in significant T1 contrast enhancement due to reduced magnetic coupling.

Ultrasound‐Triggered Delivery of Anticancer Therapeutics from MRI‐Visible Multilayer Microcapsules

AbstractAlthough imaging‐guided drug delivery represents a noninvasive alternative to both surgical resection and systemic methods, it has seen limited clinical use due to the potential toxicity and fast clearance of currently available imaging agents. Herein, we introduce theranostic biocompatible microcapsules as efficient contrast‐enhanced imaging agents that combine magnetic resonance imaging (MRI) with ultrasound‐triggered drug release for real‐time tracking and targeted delivery in vivo. The 3‐μm diameter capsules are assembled via layer‐by‐layer deposition of the natural polyphenol tannic acid and poly(N‐vinylpyrrolidone) with 4 nm iron oxide nanoparticles incorporated in the capsule wall. The nanoparticle‐modified capsules exhibit excellent T1 and T2 MRI contrast in a clinical 3T MRI scanner. Loaded with the anticancer drug doxorubicin, these capsules circulate in the blood stream for at least 48 h, which is a remarkable improvement compared to nonencapsulated nanoparticles. The application of focused ultrasound results in targeted drug release with a 16‐fold increase in doxorubicin localization in tumors compared to off‐target organs in a mouse model of breast cancer. Owing to the active contrast, long circulation, customizable size, shape, composition, and precise delivery of high payload concentrations, these materials present a powerful and safe platform for imaging‐guided precision drug delivery.

Magnetic resonance imaging contrast enhancement in vitro and in vivo by octanuclear iron-oxo cluster-based agents

A water-soluble octanuclear cluster, [Fe8], was studied with regard to its properties as a potential contrast enhancing agent in magnetic resonance imaging (MRI) in magnetic fields of 1.3, 7.2 and 11.9 T and was shown to have transverse relaxivities r2 = 4.01, 10.09 and 15.83 mM s−1, respectively. A related hydrophobic [Fe8] cluster conjugated with 5 kDa hyaluronic acid (HA) was characterized by 57Fe-Mössbauer and MALDI-TOF mass spectroscopy, and was evaluated in aqueous solutions in vitro with regard to its contrast enhancing properties [r2 = 3.65 mM s−1 (1.3 T), 26.20 mM s−1 (7.2 T) and 52.18 mM s−1 (11.9 T)], its in vitro cellular cytotoxicity towards A-549 cells and COS-7 cells and its in vivo enhancement of T2-weighted images (4.7 T) of a human breast cancer xenografted on a nude mouse. The physiologically compatible [Fe8]-HA conjugate was i.v. injected to the tumor-bearing mouse, resulting in observable, heterogeneous signal change within the tumor, evident 15 min after injection and persisting for approximately 30 min. Both molecular [Fe8] and its HA-conjugate show a strong magnetic field dependence on r2, rendering them promising platforms for the further development of T2 MRI contrast agents in high and ultrahigh magnetic fields.

MAGNETIC RESONANCE IMAGING (MRI) APPLICATION OF Fe3O4 BASED FERROFLUID SYNTHESIZED BY THERMAL DECOMPOSITION USING POLY (MALEIC ANHYDRIDE -ALT-1-OCTADECENE) (PMAO)

The Fe3O4 fluid synthesis by thermal decomposition method carried out in organic solvents with high boiling temperatures disposes a possibility of creating high-quality nanoparticles with uniform particle size and high degree of crystallization. In this paper, Fe3O4 fluid was prepared by thermal decomposition using poly (maleic anhydride-alt-1-octadecene) (PMAO) as a phase transfer ligand. The crystalline structure, morphology and magnetic property of the as-prepared samples were thoroughly characterized. The results demonstrated that the magnetic Fe3O4 nanomaterial was formed in liquid phase with spinel single phase structure, average size of 13-16 nm, and high saturation magnetization (up to 70 emu/g). Iron oxide (Fe3O4) nanoparticles coated with biocompatible poly (maleic anhydride-alt-1-octadecene) (PMAO) were synthesized for use as an MRI (magnetic resonance imaging) contrast agent. The spin-lattice (T1) and the spin-spin (T2) relaxation times of the nuclear spins (hydrogen protons) in aqueous solutions of various concentrations of coated ferrite nanoparticles were determined using a nuclear magnetic resonance (NMR) spectrometer. The MRI image was detected with higher contrast in comparison with that before injecting. By comparing with the MRI images taken in T1 weighted the T2 weighted images are clearer. The MRI images of a rabbit taken by the T2 weighted which shows that our coated ferrite nanoparticles can be used as a T2 MRI contrast agent.