High Transverse Relaxivity Research Articles

19F MRI/CEUS Dual Imaging-Guided Sonodynamic Therapy Enhances Immune Checkpoint Blockade in Triple-Negative Breast Cancer.

Treatment of highly aggressive triple-negative breast cancer (TNBC) in the clinic is challenging. Here, a liposome nanodrug (LP@PFH@HMME) integrating imaging agents and therapeutic agents for bimodal imaging-guided sonodynamic therapy (SDT) is developed, which boosted immunogenicity to enable potent immunotherapy via immune checkpoint blockade (ICB) in TNBC. In the acidic tumor microenvironment (TME), LP@PFH@HMME undergoes "nano-to-micro" transformation due to a pH-responsive lipid fusion, which makes droplets much more sensitive to ultrasound (US) in contrast-enhanced ultrasound (CEUS) and SDT studies. The nanodrug demonstrates robust bimodal imaging ability through fluorine-19 magnetic resonance imaging (19F MRI) and CEUS bimodal imaging, and it exhibits excellent solubility in aqueous solution with relatively high 19F content and desirable long transverse relaxation time (T2 = 1.072 s), making it suitable for high-performance 19F MRI, in addition to effective accumulation of nanodrugs after tail vein injection. Thus, 19F MRI/CEUS dual imaging is achievable to show adequate time points for US irradiation of tumor sites to induce highly effective SDT, which produces abundant reactive oxygen species (ROS) triggering immunogenic cell death (ICD) to assist ICB-based immunotherapy. The combination treatment design of sonodynamic therapy with immunotherapy effectively inhibited TNBC growth and recurrence, highlighting the promise of multifunctional nanodrugs in treating TNBC.

Ultrahigh-Resolution Visualization of Vascular Heterogeneity in Brain Tumors via Magnetic Nanoparticles-Enhanced Susceptibility-Weighted Imaging.

The precise assessment of vascular heterogeneity in brain tumors is vital for diagnosing, grading, predicting progression, and guiding treatment decisions. However, currently, there is a significant shortage of high-resolution imaging approaches. Herein, we propose a contrast-enhanced susceptibility-weighted imaging (CE-SWI) utilizing the minimalist dextran-modified Fe3O4 nanoparticles (Dextran@Fe3O4 NPs) for ultrahigh-resolution mapping of vasculature in brain tumors. The Dextran@Fe3O4 NPs are prepared via a facile coprecipitation method under room temperature, and exhibit small hydrodynamic size (28 nm), good solubility, excellent biocompatibility, and high transverse relaxivity (r2*, 159.7 mM-1 s-1) under 9.4 T magnetic field. The Dextran@Fe3O4 NPs-enhanced SWI can increase the contrast-to-noise ratio (CNR) of cerebral vessels to 2.5 times that before injection and achieves ultrahigh-spatial-resolution visualization of microvessels as small as 0.1 mm in diameter. This advanced imaging capability not only allows for the detailed mapping of both enlarged peritumoral drainage vessels and the intratumoral microvessels, but also facilitates the sensitive imaging detection of vascular permeability deterioration in a C6 cells-bearing rat glioblastoma model. Our proposed Dextran@Fe3O4 NPs-enhanced SWI provides a powerful imaging technique with great clinical translation potential for the precise theranostics of brain tumors.

A Minimalist Iron Oxide Nanoprobe for the High-Resolution Depiction of Stroke by Susceptibility-Weighted Imaging.

The precise mapping of collateral circulation and ischemic penumbra is crucial for diagnosing and treating acute ischemic stroke (AIS). Unfortunately, there exists a significant shortage of high-sensitivity and high-resolution in vivo imaging techniques to fulfill this requirement. Herein, a contrast enhanced susceptibility-weighted imaging (CE-SWI) using the minimalist dextran-modified Fe3O4 nanoparticles (Fe3O4@Dextran NPs) are introduced for the highly sensitive and high-resolution AIS depiction under 9.4 T for the first time. The Fe3O4@Dextran NPs are synthesized via a simple one-pot coprecipitation method using commercial reagents under room temperature. It shows merits of small size (hydrodynamic size 25.8nm), good solubility, high transverse relaxivity (r2) of 51.3 mM-1s-1 at 9.4 T, and superior biocompatibility. The Fe3O4@Dextran NPs-enhanced SWI can highlight the cerebral vessels readily with significantly improved contrast and ultrahigh resolution of 0.1mm under 9.4 T MR scanner, enabling the clear spatial identification of collateral circulation in the middle cerebral artery occlusion (MCAO) rat model. Furthermore, Fe3O4@Dextran NPs-enhanced SWI facilitates the precise depiction of ischemia core, collaterals, and ischemic penumbra post AIS through matching analysis with other multimodal MR sequences. The proposed Fe3O4@Dextran NPs-enhanced SWI offers a high-sensitivity and high-resolution imaging tool for individualized characterization and personally precise theranostics of stroke patients.

PH-Responsive magnetic nanocarriers for chelator-free bimodal (MRI/SPECT-CT) image-guided chemo-hyperthermia therapy in human breast carcinoma.

Although chemotherapy with magnetic nanocarriers has witnessed significant advancement in the field of cancer treatment, multimodal diagnosis and combinatorial therapy using a single nanoplatform will have much better efficacy in achieving superior results. Herein, we constructed a smart theranostic system by combining pH-sensitive tartaric acid-stabilized Fe3O4 magnetic nanocarriers (TMNCs) with SPECT imaging and a chemotherapeutic agent for image-guided chemo-hyperthermia therapy. The carboxyl-enriched exteriors of TMNCs provided sites for the conjugation of a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and radiolabeling (141Ce). The usage of 145.4 keV gamma rays made this platform an ideal choice for in vivo SPECT-CT imaging, showing the retention of the nanoformulation in the tumor site even after 28 days. Further, TMNCs showed a very high transverse relaxation rate (r2) of 171 mM-1 s-1, which is higher than that of clinically approved magnetic resonance imaging (MRI) contrast agents such as ferumoxtran (65 mM-1 s-1) and ferumoxides (120 mM-1 s-1). Further, the developed drug-loaded hybrid platform showed significantly higher cytotoxicity towards breast cancer cells, which was augmented by in vitro magnetic hyperthermia. Bright-field microscopy and cell cycle analysis suggested that cell death occurred through induction of G2-M arrest and subsequent apoptosis. These findings clearly suggest the potential of the developed hybrid nanoplatform for image-guided combination therapy.

SERS and MRS signals engineered dual-mode aptasensor for simultaneous distinguishment of aflatoxin subtypes

The accurate monitoring of aflatoxin subtypes is vitally important for food safety. Herein, a dual-mode aptasensor with surface-enhanced Raman scattering (SERS) and magnetic relaxation switching (MRS) signals is developed for the detection of aflatoxin B1, B2 and M1 (i.e. AFB1, AFB2 and AFM1). Au-Ag Janus NPs and Au-mushroom NPs are prepared and show intense and non-interfering SERS peaks without the additional modification of Raman molecules, and are utilized as SERS nanotags for the distinguishment of AFB1 and AFB2. Fe3O4@Au NPs functionalized by AFM1 aptamers are applied as MRS nanoprobes for the monitoring of AFM1. Aptamers engineered SERS nanotags and MRS nanoprobes are assembled, and show strong SERS performances and high transverse relaxation time (T2). AFB1, AFB2 and AFM1 induce the separation of SERS nanotags from the assemblies and the dispersion of Fe3O4@Au NPs, resulting in the decrease of SERS signals at 1278 cm−1 and 1000 cm−1 as well as the reduction of T2 values. The dual-mode but three kinds of detection signals don’t interfere with each other and exhibit a significant linear relationship with the concentration of targets. This platform provides a high throughput monitoring strategy for the simultaneous analysis of different subtypes of mycotoxin.

N-Acetylcysteine-Loaded Magnetic Nanoparticles for Magnetic Resonance Imaging.

Acute respiratory distress syndrome (ARDS) is a life-threatening condition characterized by the rapid onset of lung inflammation Therefore, monitoring the spatial distribution of the drug directly administered to heterogeneously damaged lungs is desirable. In this work, we focus on optimizing the drug N-acetylcysteine (NAC) adsorption on poly-l-lysine-modified magnetic nanoparticles (PLLMNPs) to monitor the drug spatial distribution in the lungs using magnetic resonance imaging (MRI) techniques. The physicochemical characterizations of the samples were conducted in terms of morphology, particle size distributions, surface charge, and magnetic properties followed by the thermogravimetric quantification of NAC coating and cytotoxicity experiments. The sample with the theoretical NAC loading concentration of 0.25 mg/mL was selected as an optimum due to the hydrodynamic nanoparticle size of 154 nm, the surface charge of +32 mV, good stability, and no cytotoxicity. Finally, MRI relaxometry confirmed the suitability of the sample to study the spatial distribution of the drug in vivo using MRI protocols. We showed the prevailing transverse relaxation with high transverse relaxivity values and a high r2(*)/r1 ratio, causing visible hypointensity in the final MRI signal. Furthermore, NAC adsorption significantly affects the relaxation properties of PLLMNPs, which can help monitor drug release in vitro/in vivo.

Highly improved pH-Responsive anticancer drug delivery and T2-Weighted MRI imaging by magnetic MOF CuBTC-based nano/microcomposite.

Cu-BTC framework has received a considerable attention in recent years as a drug carrier candidate for cancer treatment due to its unique structural properties and promising biocompatibility. However, its intrinsic deficiency for medical imaging potentially limits its bioapplications; To address this subject, a magnetic nano/microscale MOF has been successfully fabricated by introducing Fe3O4 nanoparticles as an imaging agent into the porous isoreticular MOF [Cu3(BTC)2] as a drug carrier. The synthesized magnetic MOFs exhibits a high loading capacity (40.5%) toward the model anticancer DOX with an excellent pH-responsive drug release. The proposed nanocomposite not only possesses large surface area, high magnetic response, large mesopore volume, high transverse relaxivity (r 2) and good stability but also exhibits superior biocompatibility, specific tumor cellular uptake, and significant cancer cell viability inhibitory effect without any targeting agent. It is expected that the synthesized magnetic nano/microcomposite may be used for clinical purposes and can also serve as a platform for photoactive antibacterial therapy ae well as pH/GSH/photo-triple-responsive nanocarrier.

Gadolinium-doped fluorescent carbon quantum dots as MRI contrast agents and fluorescent probes

In this research passivated gadolinium-doped carbon quantum dots (Gd-doped CQDs) were synthesized from starch by a hydrothermal method. The X-ray diffraction (XRD) pattern of the Gd-doped CQDs showed the formation of highly amorphous carbon. The Fourier transform infrared spectroscopy (FTIR) results suggested that the CQDs are functionalized with C-N and N–H bonds. The synthesized CQDs with a size distribution of 2–8 nm have an absorption peak at 271 nm in UV–Visible spectroscopy (UV–Vis). The photoluminescence (PL) in CQDs was dependent on the excitation wavelength. The QY of the synthesized CQDs was calculated to be 13.2%. The Gd-doped CQDs exhibited sustained PL in ionic solutions with different ionic strengths and different temperatures up to 65 °C. Fluorescence imaging on mouse C34/connective tissue-L929 cells confirmed that Gd-doped CQDs could be well distributed over the cytoplasm. The magnetic resonance imaging (MRI) showed that the Gd-doped CQDs have extremely high longitudinal and transverse relaxivity values of as high as 218.28 mM−1 s−1 and 364.68 mM−1 s−1. The synthesized Gd-doped CQDs are promising candidates as multifunctional imaging probes and MRI contrast agents in biomedical diagnosis and brain mapping applications.

Characterization of commercial iron oxide clusters with high transverse relaxivity

Clusters of iron oxide particles are excellent contrast agents for molecular and cellular MRI because of their large effect on water proton transverse relaxation. Their efficiency depends on the magnetization of the particles, the size of the cluster and the intra-aggregate volume fraction occupied by the iron oxide particles inside the cluster. After optimization of these different parameters, a relaxivity of ∼ 750 s−1mM−1 can theoretically be achieved. Polymag࣪™ clusters are initially intended for magnetofection but are here shown to present excellent relaxation properties. Magnetometry shows that the particles constituting the clusters have a high saturation magnetization (Mv = 371000 A/m) and present a broad log-normal size distribution (d0,c = 4.9 and σ = 0.53). The clusters have a hydrodynamic diameter of 180 nm and also present a large polydispersity index (PDI = 0.15). The transverse relaxivity of the clusters is remarkably high: r2 = 470 s−1mM−1 at 1.41 T and 37°C. As their relaxation properties are independent of temperature and interecho time, the clusters should be mainly in the Static Dephasing Regime (SDR), even if some large clusters are probably closer to the Partial Refocusing Model (PRM), as suggested by the large estimated ΔωtτD ∼ 55. Since they present a large magnetic moment, the Polymag™ clusters are sensitive to the magnetic field of the NMR device, in which they probably form linear chains: a reversible increase of the relaxation times is observed after the insertion in the NMR system. They could be good candidates for cellular imaging since they should be easily internalized in cells using the magnetofection protocol and then easily detected by MRI thanks to their high relaxivity.

Hierarchical iron oxide nanocomposite: Bundle-like morphology, magnetic properties and potential biomedical application

Controlled spatial arrangements of superparamagnetic iron oxide nanoparticles (SPIONs) in complex nanostructures determine fine tuning of physico-chemical properties which, in turn, may lead to new practical applications. We report here on newly observed properties of hierarchical SPIONs nanostructure with bundle-like morphology, also known as nanobundles. Colloidal chemical processes and sol-gel synthesis were used for the synthesis of nanobundles, i.e. i) self-assembly of SPIONs into magnetic nanoparticle clusters, ii) their magnetic assembly to the nanochains, and finally iii) formation of bundle-like hierarchical nanostructure. An XRPD measurements show spinel crystal structure of maghemite/magnetite nanoparticles, EDS analysis reveals Fe, Si and O as main elements whereas SEM/TEM analysis show silica-coated magnetic nanoclusters (∼100 nm) and their hierarchical assemblies with bundle-like morphology of ∼8 μm length and ∼1 μm width. TEM analysis revealed core-shell nature of iron oxide nanoparticle clusters with their size of around 80 nm that were coated by an amorphous silica shell with thickness of ∼15 nm. The nanoclusters in the core are constructed of maghemite/magnetite nanoparticle assembly with primary iron oxide nanoparticle size about 10 nm. The magnetization M data as a function of an applied external magnetic field H were successfully fitted by the Langevin function, whence the magnetic moment μp = 19256 μB, and the diameter d = 9.6 nm of nanoparticles were determined. Microsized bundle-like particles are superparamagnetic, magnetically guidable and possess high transverse relaxivity of r2 = 397.8 mM−1s−1. Magnetic properties and such high value of transverse relaxivity holds promise for nanobundles application in MRI imaging (MRI contrast agent), as nanobundles may enhance the magnetic field in their surroundings and enhance proton relaxation processes. Our nanobundles can open new opportunities in the biomedical applications, magnetic separation, photonic crystals and magnetic liquid manipulation and can be inspiration for synthesizing novel self-assembled nanoparticle structures.

Multimodal Contrast Agent Enabling pH Sensing Based on Organically Functionalized Gold Nanoshells with Mn-Zn Ferrite Cores.

Highly complex nanoparticles combining multimodal imaging with the sensing of physical properties in biological systems can considerably enhance biomedical research, but reports demonstrating the performance of a single nanosized probe in several imaging modalities and its sensing potential at the same time are rather scarce. Gold nanoshells with magnetic cores and complex organic functionalization may offer an efficient multimodal platform for magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and fluorescence techniques combined with pH sensing by means of surface-enhanced Raman spectroscopy (SERS). In the present study, the synthesis of gold nanoshells with Mn-Zn ferrite cores is described, and their structure, composition, and fundamental properties are analyzed by powder X-ray diffraction, X-ray fluorescence spectroscopy, transmission electron microscopy, magnetic measurements, and UV-Vis spectroscopy. The gold surface is functionalized with four different model molecules, namely thioglycerol, meso-2,3-dimercaptosuccinate, 11-mercaptoundecanoate, and (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide, to analyze the effect of varying charge and surface chemistry on cells in vitro. After characterization by dynamic and electrophoretic light scattering measurements, it is found that the particles do not exhibit significant cytotoxic effects, irrespective of the surface functionalization. Finally, the gold nanoshells are functionalized with a combination of 4-mercaptobenzoic acid and 7-mercapto-4-methylcoumarin, which introduces a SERS active pH sensor and a covalently attached fluorescent tag at the same time. 1H NMR relaxometry, fluorescence spectroscopy, and PAI demonstrate the multimodal potential of the suggested probe, including extraordinarily high transverse relaxivity, while the SERS study evidences a pH-dependent spectral response.

Visualizing the Potential Impairment of Polymyxin B to Central Nervous System Through MR Susceptibility-Weighted Imaging.

Polymyxin B (PMB) exert bactericidal effects on the cell wall of Gram-negative bacteria, leading to changes in the permeability of the cytoplasmic membrane and resulting in cell death, which is sensitive to the multi-resistant Gram-negative bacteria. However, the severe toxicity and adverse side effects largely hamper the clinical application of PMB. Although the molecular pathology of PMB neurotoxicity has been adequately studied at the cellular and molecular level. However, the impact of PMB on the physiological states of central nervous system in vivo may be quite different from that in vitro, which need to be further studied. Therefore, in the current study, the biocompatible ultra-uniform Fe3O4 nanoparticles were employed for noninvasively in vivo visualizing the potential impairment of PMB to the central nervous system. Systematic studies clearly reveal that the prepared Fe3O4 nanoparticles can serve as an appropriate magnetic resonance contrast agent with high transverse relaxivity and outstanding biosafety, which thus enables the following in vivo susceptibility-weighted imaging (SWI) studies on the PMB-treated mice models. As a result, it is first found that the blood-brain barrier (BBB) of mice may be impaired by successive PMB administration, displaying by the discrete punctate SWI signals distributed asymmetrically across brain regions in brain parenchyma. This result may pave a noninvasive approach for in-depth studies of PMB medication strategy, monitoring the BBB changes during PMB treatment, and even assessing the risk after PMB successive medication in multidrug-resistant Gram-negative bacterial infected patients from the perspective of medical imaging.

Activated Platelet-Homing Nanoplatform for Targeting Magnetic Resonance Imaging of Aneurysm-Related Thrombus in Rabbits.

Thrombosis is closely related to the instability of intracranial aneurysm (IA), whose rupture is associated with high morbidity and mortality. It is difficult to detect an IA-related thrombus because traditional magnetic resonance imaging (MRI) and even contrast-enhanced MRI cannot clearly distinguish a thrombus from the surrounding tissues. Herein, a nanoplatform [(MFe2O4-ZnDPA nanoparticles (NPs)], consisting of Zn0.4Co0.6Fe2O4@Zn0.4Mn0.6Fe2O4 NPs for imaging and Zn(II)-bis(dipicolylamine) (ZnDPA) for thrombus targeting, is constructed to target an experimental aneurysm-related thrombus in rabbits via MRI. In vitro experiments including platelet safety evaluation primarily prove that MFe2O4-ZnDPA NPs with a high MRI transverse relaxation time (T2) have good biocompatibility. MFe2O4-ZnDPA NPs could target a thrombus via the special interaction between ZnDPA and phosphatidylserine of activated platelets in the thrombus through MRI and Fe quantification assays. Moreover, after MFe2O4-ZnDPA NPs are injected into the ear vein of common carotid artery aneurysm model rabbits, MRI shows that MFe2O4-ZnDPA NPs could accumulate in the aneurysm-related thrombus from 0 to 15 min after injection and decrease in the next 45 min. Meanwhile, MFe2O4-ZnDPA NPs could decrease the MRI T2 signal of the aneurysm-related thrombus to enhance the outline of the aneurysm. This study demonstrates that a nanoplatform can enhance the detection of an aneurysm-related thrombus as well as aneurysm itself to assist further treatment of IA.

Manganese and dysprosium codoped carbon quantum dots as a potential fluorescent/T1/T2/CT quadri-modal imaging nanoprobe

It has been challenging to integrate various medical imaging modalities into an ultra-small nanoparticle with good biocompatibility to build highly efficient multimodal imaging nanoprobes. A new manganese and dysprosium codoped carbon quantum dots (Mn,Dy-CQDs) with a mean diameter of 1.77 nm was synthesized for fluorescence imaging, T1/T2-weighted magnetic resonance imaging (T1/T2-weighted MRI), and x-ray computed tomography (CT) imaging using a simple one-step hydrothermal approach. The obtained Mn,Dy-CQDs showed good water solubility, long-term stability, strong stable fluorescence property (fluorescence quantum yield of 31.62%), and excellent biocompatibility. The cell imaging verified that the Mn,Dy-CQDs have high efficiency of fluorescence imaging. The Mn,Dy-CQDs, on the other hand, had a superior x-ray absorption performance (47.344 HU l g−1), a higher longitudinal relaxivity (r 1 = 7.47 mM−1 s−1), a higher transverse relaxivity (r 2 = 42.686 mM−1 s−1). In vitro T1/T2-weighted MRI and CT imaging showed that Mn,Dy-CQDs can produce a strong contrast enhancement impact. To summarise, the Mn,Dy-CQDs may be used as a T1/T2-weighted MRI/CT/fluorescent quadri-modal imaging nanoprobe, indicating that they have a lot of uses in biomedical multimode imaging and clinics.

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.

Manganese Ferrite Nanoparticles Encapsulated into Vitamin E/Sphingomyelin Nanoemulsions as Contrast Agents for High-Sensitive Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is one of the most powerful non-invasive imaging modalities used in clinics due to its great spatial resolution and excellent soft-tissue contrast, though still less sensitive than other techniques such as the nuclear imaging modalities. This lack of sensitivity can be improved with the use of contrast agents based on nanomaterials. In recent years, researchers have focused on the development of magnetic nanoparticles, given their role as enhancers of the contrast signal based on the magnetic resonance. Manganese ferrite nanoparticles stand out, given their high magnetic susceptibility and magnetic soft nature. Herein, 10nm MnFe2 O4 nanoparticles, functionalized with the natural antioxidant vitamin E (VitE-MFO) are encapsulated into simple, biodegradable and non-toxic nanoemulsions (NEs), by a reproducible one-step method obtaining stable 150nm-sized magnetic nanoemulsions (VitE-MFO-NEs). After encapsulation, the superparamagnetic properties of VitE-MFO are maintained and MR imaging studies reveal an extremely high transverse relaxivity for VitE-MFO-NEs (652.9×10-3 m-1 s-1 ), twofold higher than VitE-MFO value. Moreover, VitE-MFO-NEs show great in vivo biocompatibility and good signal in in vivo and ex vivo MRI, which indicates their great potential for biomedical imaging enhancing the negative MR contrast and significantly improving the sensitivity of MRI.

Polypyrrole-Coated Magnetite Vortex Nanoring for Hyperthermia-Boosted Photothermal/Magnetothermal Tumor Ablation Under Photoacoustic/Magnetic Resonance Guidance.

Photothermal/magnetothermal-based hyperthermia cancer therapy techniques have been widely investigated, and associated nanotechnology-assisted treatments have shown promising clinical potentials. However, each method has some limitations, which have impeded extensive applications. For example, the penetration ability of the photothermal is not satisfactory, while the heating efficiency of the magnetothermal is very poor. In this study, a novel magnetite vortex nanoring nanoparticle-coated with polypyrrole (denoted as nanoring Fe3O4@PPy-PEG) was first synthesized and well-characterized. By combining photothermal and magnetothermal effects, the performance of the dual-enhanced hyperthermia was significantly improved, and was thoroughly examined in this study. Benefiting from the magnetite vortex nanoring and polypyrrole, Fe3O4@PPy-PEG showed excellent hyperthermia effects (SAR = 1,648 Wg–1) when simultaneously exposed to the alternating magnetic field (300 kHz, 45 A) and near-infrared (808 nm, 1 W cm–2) laser. What is more, nanoring Fe3O4@PPy-PEG showed a much faster heating rate, which can further augment the antitumor effect by incurring vascular disorder. Besides, Fe3O4@PPy-PEG exhibited a high transverse relaxation rate [60.61 mM–1 S–1 (Fe)] at a very low B0 field (0.35 T) and good photoacoustic effect. We believe that the results obtained herein can significantly promote the development of multifunctional nanoparticle-mediated magnetic and photo induced efficient hyperthermia therapy.

Repurposing Ferumoxytol as a Breast Cancer-Associated Macrophage Tracer with Five-Dimensional Quantitative [Fe]MRI of SPION Dynamics.

Simple SummaryWith the incorporation of immune-modulating therapies into the standard management of triple-negative breast cancer, there is increased interest in the non-invasive imaging of the tumor immune microenvironment. Ferumoxytol is FDA-approved as an iron replacement therapy for iron-deficiency anemia and is also a superparamagnetic iron oxide nanoparticle (SPION) resulting in negative enhancement on T2-weighted MR imaging. It has previously been established that ferumoxytol is taken up by macrophages. In the current study, we used ferumoxytol-contrasted MRI to quantitatively image the iron concentration, and, by extension, the tumor-associated macrophage infiltration within the tumor microenvironment of a highly inflammatory model of triple-negative breast cancer.Tumor-associated macrophages (TAMs) in breast cancer regulate inflammation, immunosuppression, angiogenesis, and metastasis. However, TAM imaging remains a clinical challenge. Ferumoxytol has long been an FDA-approved superparamagnetic iron oxide nanoparticle (SPION) preparation used as an intravenous (IV) treatment for iron-deficiency anemia. Given its high transverse relaxivity, ferumoxytol produces a negative image contrast upon cellular uptake in T2-weighted magnetic resonance imaging (MRI) studies. Here we evaluated ferumoxytol as a contrast agent to image/quantify TAMs in an aggressive mouse model of breast cancer: We developed [Fe]MRI to measure the 5-dimensional function c(x,y,z,t), where c is the concentration of nanoparticle iron and {x,y,z,t} is the 4-dimensional set of tumor space-time coordinates. Ferumoxytol SPIONs are readily phagocytosed (~104/cell) by the F4/80+CD11b+ TAMs within breast tumors. Quantitative [Fe]MRIs served to determine both the spatial and the temporal distribution of the SPION iron, and hence to measure [Fe] = c(x,y,z,t), a surrogate for TAM density. In single-dose pharmacokinetic studies, after an IV dose of 5 mg/Kg iron, [Fe]MRI measurements showed that c(x,y,z,t) within breast tumors peaked around [Fe] = 70 μM at 42 h post-administration, and decayed below the [Fe]MRI detection limit (~2 μM) by day 7. There was no SPION uptake in control organs (muscle and adipose tissue). Optical microscopy of tissue sections confirmed that F4/80+CD11b+ TAMs infiltrated the tumors and accumulated SPION iron. Our methodology and findings have translational applications for breast cancer patients.

T2- and T1 relaxivities and magnetic hyperthermia of iron-oxide nanoparticles combined with paramagnetic Gd complexes

The present paper reports the synthesis of iron-oxide nanoparticles (diameter 12.8±2.2 nm) coated with silica shell doped with paramagnetic Gd(III)-based complexes. The resulting nanoparticles with a silica shell thickness of about 45 nm have an average diameter of 113.1±14.3 nm and feature high transverse and longitudinal relaxivities (356 and 25 mM−1 s−1, respectively) at 1.5 T and 25 °C on a medical whole body NMR scanner. It has been also revealed using magnetic heating measurements that the prepared core-shell nanoparticles possess a high specific adsorption rate of around 236 W/g in aqueous media. The surface of the composite nanoparticles was decorated by amino-groups for a greater cellular uptake behaviour. The cell viability measurements reveal the concentration-dependent cytotoxicity of the nanoparticles, which agrees well with the high content of Gd(III) complexes in the nanomaterial. The obtained results show that the core-shell design of nanoparticles with superparamagnetic and paramagnetic parts can be promising for high transverse (and longitudinal) relaxivity as well as magnetic hyperthermia.

Developing A Novel Coumarone-Phenyl Amide Functionalized [Gd(III)-Pt(IV)] Complex as High T1, T2 Relaxive M-MRI Contrast Agent for Cancer Diagnosis

Pt(IV) cored Gd(III) metal complex as a multimodal MRI contrast agent for cancer diagnosis is reported. The hetero nuclear complex [Pr-(DO3-Ch-Ph-Am-Gd(III))2Pt(II)] is highly soluble in water and stable at room temperature. The complex shows high longitudinal (r1p = 24.43 mM-1 s-1) and transversal (r2p = 38.61 mM-1 s-1) relaxivity values in neat aqueous solution at pH =7 and at 27 oC. The relaxivity value of the complex is greater than the low molecular weight, FDA approved MRI contrast agents. The presence of two water molecules in the first coordination sphere and a replaceable hydrogen atom in the linker enhances the proton relaxation rate and gives a huge relaxivity value. The r2p/r1P ratio of 1.58 confirms that the complex is a T1-weighted contrast agent. The presence of high polar coumarone pendant arm and high rigid acridone moieties in the complex make the complex as better anticancer agent for ovarian cancer. The high polar nature of the coumarone, phenyl amide, acridone moiety will show better binding efficiency with ovarian cancer creating CA125 glycoprotein.