T2 Dual-modal Magnetic Resonance Imaging Research Articles

Tannic acid-mediated synthesis of flower-like mesoporous MnO2 nanostructures as T1–T2 dual-modal MRI contrast agents and dual-enzyme mimetic agents

This study introduces a simple method for preparing a new generation of MnO2 nanomaterials (MNMs) using tannic acid as a template. Two shapes of MnO2 NMs, flower-like M1-MnO2 and near-spherical M2-MnO2, were prepared and compared as dual-active nanozymes and contrast agents in magnetic resonance imaging (MRI). Various parameters, including the crystallinity, morphology, magnetic saturation (Ms), surface functionality, surface area, and porosity of the MNMs were investigated. Flower-like M1-MnO2 NMs were biocompatible and exhibited pH-sensitive oxidase and peroxidase mimetic activity, more potent than near-spherical M2-MnO2. Furthermore, the signal intensity and r1 relaxivity strongly depended on the crystallinity, morphology, pore size, and specific surface area of the synthesized MNMs. Our findings suggest that flower-like M1-MnO2 NM with acceptable dual-enzyme mimetic (oxidase-like and peroxidase-like) and T1 MRI contrast activities could be employed as a promising theranostic system for future purposes.

Parameterisation and cellular evaluation of poly(ethylene) oxide-coated erbium oxide in MCF-7 cells as MRI diagnostic nanofibres

The novelty of this work is the conjugation of poly(ethylene) oxide (PEO) with the erbium oxide (Er2O3) nanoparticles using the electrospinning technique. In this work, synthesised PEO-coated Er2O3 nanofibres were characterised and evaluated for their cytotoxicity to assess their potential use as diagnostic nanofibres for magnetic resonance imaging (MRI). PEO has significantly impacted nanoparticle conductivity due to its lower ionic conductivity at room temperature. The findings showed that the surface roughness was improved over the nanofiller loading, implying an improvement in cell attachment. The release profile performed for drug-controlling purposes has demonstrated a stable release after 30 min. Cellular response in MCF-7 cells showed high biocompatibility of the synthesised nanofibres. The cytotoxicity assay results showed that the diagnostic nanofibres had excellent biocompatibility, indicating the feasibility for diagnosis purposes. With excellent contrast performance, the PEO-coated Er2O3 nanofibres developed novel T2 and T1-T2 dual-mode MRI diagnostic nanofibres leading to better cancer diagnosis. In conclusion, this work has demonstrated that the conjugation of PEO-coated Er2O3 nanofibres improved the surface modification of the Er2O3 nanoparticles as a potential diagnostic agent. Using PEO in this study as a carrier or polymer matrix significantly influenced the biocompatibility and internalisation efficiency of the Er2O3 nanoparticles without triggering any morphological changes after treatment. This work has suggested permissible concentrations of PEO-coated Er2O3 nanofibres for diagnostic uses.

Poly(ethylene) oxide/erbium oxide as T2 and T1-T2 dual-mode MRI diagnostic nanofibres

A novel magnetic resonance imaging (MRI) diagnostic nanofibres were synthesised using Er2O3 nanoparticles (2% to 8%) embedded in the PEO matrix via electrospinning. The prepared PEO/Er2O3 nanofibres were fully characterised, and the magnetic relaxivity study for MRI contrast enhancement was evaluated. The findings showed that the fibre diameter became broader with increasing nanofiller loading. The encapsulation of Er2O3 nanoparticles in PEO fibres demonstrated excellent entrapment efficiency using the electrospinning method. The reduction of the crystallinity index provoked changes in the crystallite size, thus contributing to the amorphous component. The addition of Er2O3 nanoparticles in the PEO matrix demonstrated the changes in the conformational structure of the peak intensity, shape and position of the C–O–C stretching absorptions. PEO/Er2O3 nanofibres have successfully demonstrated potential T2 and T1-T2 dual-mode diagnostic nanofibres in MRI 1.5 T. Therefore, it is considered a great achievement in the detection sensitivity for cancer diagnosis due to its potential diagnostic use that can be activated in two-way.

Single-Atom Gd Nanoprobes for Self-Confirmative MRI with Robust Stability.

Gadolinium (Gd)-based complexes are extensively utilized as contrast agents (CAs) in magnetic resonance imaging (MRI), yet, suffer from potential safety concerns and poor tumor targeting. Herein, as a mimic of Gd complex, single-atom Gd nanoprobes with r1 and r2 values of 34.2 and 80.1 mM-1 s-1 (far higher than that of commercial Gd CAs) at 3 Tareconstructed, which possessed T1 /T2 dual-mode MRI with excellent stability and good tumor targeting ability. Specifically, single-atom Gdisanchored on nitrogen-doped carbon matrix (Gd-Nx C) through spatial-confinement method, whichisfurther subjected to controllable chemical etching to afford fully etched bowl-shape Gd-Nx C (feGd-Nx C) with hydrophilic properties and defined coordination structure, similar to commercial Gd complex. Such nanostructures not only maximized the Gd3+ site exposure, but alsoaresuitable for self-confirmative diagnosis through one probe with dual-mode MRI. Moreover, the strong electron localization and interaction between Gd and N atoms afforded feGd-Nx C excellent kinetic inertness and thermal stability (no significant Gd3+ leachingisobserved even incubated with Cu2+ and Zn2+ for two months), providing a creative design protocol for MRI CAs.

PDGFB-targeted functional MRI nanoswitch for activatable T1–T2 dual-modal ultra-sensitive diagnosis of cancer

As one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off–on T1–T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1–T2 dual-mode MRI signals. The tumor-specific off–on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off–on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes.

Self-Confirming Magnetosomes for Tumor-Targeted T1 /T2 Dual-Mode MRI and MRI-Guided Photothermal Therapy.

Nanomaterials as T1 /T2 dual-mode magnetic resonance imaging (MRI) contrast agents have great potential in improving the accuracy of tumor diagnosis. Applications of such materials, however, are limited by the complicated chemical synthesis process and potential biosafety issues. In this study, the biosynthesis of manganese (Mn)-doped magnetosomes (MagMn) that not only can be used in T1 /T2 dual-mode MR imaging with self-confirmation for tumor detection, but also improve the photothermal conversion efficiency for MRI-guided photothermal therapy (PTT) is reported. The MagMn nanoparticles (NPs) are naturally produced through the biomineralization of magnetotactic bacteria by doping Mn into the ferromagnetic iron oxide crystals. In vitro and in vivo studies demonstrated that targeting peptides functionalized MagMn enhanced both T1 and T2 MRI signals in tumor tissue and significantly inhibited tumor growth by the further MRI-guided PTT. It is envisioned that the biosynthesized multifunctional MagMn nanoplatform may serve as a potential theranostic agent for cancer diagnosis and treatment.

Orchestrated Yolk-Shell Nanohybrids Regulate Macrophage Polarization and Dendritic Cell Maturation for Oncotherapy with Augmented Antitumor Immunity.

The protumoral and immunosuppressive tumor microenvironments greatly limit the antitumor immune responses of nanoparticles for cancer immunotherapy. Here, the intrinsic immunomodulatory effects of orchestrated nanoparticles and their ability to simultaneously trigger tumor antigen release, thereby reversing immunosuppression and achieving potent antitumor immunity and augmented cancer therapy, are explored. By optimizing both the composition and morphology, a facile strategy is proposed to construct yolk-shell nanohybrids (Fe3 O4 @C/MnO2 -PGEA, FCMP). The intrinsic immunomodulatory effects of FCMP are utilized to reprogram macrophages to M1 phenotype and induce the maturation of dendritic cells. In addition, the chemical, magnetic, and optical properties of FCMP contribute to amplified immunogenic cell death induced by multiaugmented chemodynamic therapy (CDT) and synergistic tumor treatment. Taking advantage of the unique yolk-shell structure, accurate T1 -T2 dual-mode magnetic resonance imaging can be realized and CDT can be maximized through sufficient exposure of both the Fe3 O4 core and MnO2 shell. Potent antitumor effects are found to substantially inhibit the growth of both primary and distant tumors. Furthermore, the strategy can be extended to the synthesis of other yolk-shell nanohybrids with tailored properties. This work establishes a novel strategy for the fabrication of multifunctional nanoplatforms with yolk-shell structure for effective cancer therapy with immunomodulation-enhanced antitumor immunity.

Integration of PEG-conjugated gadolinium complex and superparamagnetic iron oxide nanoparticles as T 1-T 2 dual-mode magnetic resonance imaging probes.

The T1−T2 dual-mode probes for magnetic resonance imaging (MRI) can non-invasively acquire comprehensive information of different tissues or generate self-complementary information of the same tissue at the same time, making MRI a more flexible imaging modality for complicated applications. In this work, three Gadolinium-diethylene-triaminepentaaceticacid (Gd-DTPA) complex conjugated superparamagnetic iron oxide (SPIO) nanoparticles with different Gd/Fe molar ratio (0.94, 1.28 and 1.67) were prepared as T1–T2 dual-mode MRI probes, named as SPIO@PEG-GdDTPA0.94, SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67, respectively. All SPIO@PEG-GdDTPA nanocomposites with 8 nm spherical SPIO nanocrystals showed good Gd3+ chelate stability. SPIO@PEG-GdDTPA0.94 nanocomposites with lowest Gd/Fe molar ratio show no cytotoxicity to Raw 264.7 cells as compared to SPIO@PEG-GdDTPA1.28 and SPIO@PEG-GdDTPA1.67. SPIO@PEG-GdDTPA0.94 nanocomposites with r1 (8.4 mM−1s−1), r2 (83.2 mM−1s−1) and relatively ideal r2/r1 ratio (9.9) were selected for T1–T2 dual-mode MRI of blood vessels and liver tissue in vivo. Good contrast images were obtained for both cardiovascular system and liver in animal studies under a clinical 3 T scanner. Importantly, one can get high-quality contrast-enhanced blood vessel images within the first 2 h after contrast agent administration and acquire liver tissue anatomy information up to 24 h. Overall, the strategy of one shot of the dual mode MRI agent could bring numerous benefits not only for patients but also to the radiologists and clinicians, e.g. saving time, lowering side effects and collecting data of different organs sequentially.

One Responsive Stone, Three Birds: Mn(III)-Hemoporfin Frameworks with Glutathione-Enhanced Degradation, MRI, and Sonodynamic Therapy.

Ultrasound-driven sonodynamic therapy (SDT) catches numerous attentions for destroying deep-seated tumors, but its applications suffer from unsatisfactory therapeutic effects and metabolism. Furthermore, SDT is usually weakened by the complex tumor microenvironment, such as the overexpression of glutathione (GSH). To address these issues, Mn(III)-hemoporfin frameworks (Mn(III)-HFs) are reported as nanosonosensitizers by using biocompatible hematoporphyrin monomethyl-ether (HMME) to coordinate with Mn(III) ions. Mn(III)-HFs/PEG can react with GSH to produce Mn(II) ions and oxidized glutathione (GSSG), resulting in three fascinating features: 1) the redox reaction facilitates the decomposition of Mn(III)-HFs/PEG and then collapse of nanostructures, improving the biodegradability; 2) Mn(II) ions with five unpaired 3d-electrons exhibit better magnetic resonance imaging (MRI) ability compared to Mn(III) ions with four electrons; 3) both the depletion of endogenous GSH and the dissociated HMME boost 1 O2 generation ability under US irradiation. As a result, when Mn(III)-HFs/PEG dispersion is intravenously administered into mice, it exhibits high-contrast T1 /T2 dual-modal MRI and significant suppression for the growth rate of the deep-seated tumor. Furthermore, Mn(III)-HFs/PEG can be efficiently metabolized from the mice. Therefore, Mn(III)-HFs/PEG exhibit GSH-enhanced degradation, MRI, and SDT effects, which provide some insights on the developments of other responsive nanosonosensitizers.

Cyclic RGD functionalized liposomes targeted to activated platelets for thrombosis dual-mode magnetic resonance imaging.

Thrombotic disease is a serious threat to human health. The rapid and accurate detection of thrombosis is still a clinical challenge. To achieve the accurate diagnosis of thrombosis with magnetic resonance imaging (MRI), nanomaterials-based contrast agents have been developed in recent years. In this study, cyclic RGD functionalized liposomes targeted to the activated platelets are developed for thrombosis dual-mode MRI. The cyclic RGD functionalized liposomes (cRGD@MLP-Gd) encapsulated with gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) and superparamagnetic iron oxide (SPIO) are prepared, and their thrombus-targeted T1 and T2 MRI potential is evaluated in vitro and in vivo. Results show that cRGD@MLP-Gd could actively bind to the activated platelets and gradually accumulate at the thrombus site with a T1 - T2 contrast enhancement imaging effect in vitro. In in vivo MRI experiments, cRGD@MLP-Gd exhibits a T2 contrast enhancement at 1 h after intravenous administration, followed by a visibly larger T1 contrast enhancement at the thrombus site. This dynamic property showed that cRGD@MLP-Gd could actively bind to thrombus and possessed an enhanced T1 and T2 dual-mode MRI effect in vivo. Our results establish the characterization, feasibility and superiority of cRGD@MLP-Gd for the rapid identification of thrombosis, showing great potential to improve diagnostic accuracy and sensitivity to thrombosis of the MRI technique.

An Albumin-Binding T1- T2 Dual-Modal MRI Contrast Agents for Improved Sensitivity and Accuracy in Tumor Imaging.

Magnetic resonance imaging (MRI) diagnosis is better assisted by contrast agents that can augment the signal contrast in the imaging appearance. However, this technique is still limited by the inherently low sensitivity on the recorded signal changes in conventional T1 or T2 MRI in a qualitative manner. Here, we provide a new paradigm of MRI diagnosis using T1- T2 dual-modal MRI contrast agents for contrast-enhanced postimaging computations on T1 and T2 relaxation changes. An albumin-binding molecule (i.e., truncated Evans blue) chelated with paramagnetic manganese ion was developed as a novel T1- T2 dual-modal MRI contrast agent at high magnetic field (7 T). Furthermore, the postimaging computations on T1- T2 dual-modal MRI led to greatly enhanced signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) in both subcutaneous and orthotopic brain tumor models compared with traditional MRI methods. The T1- T2 dual-modal MRI computations have great potential to eliminate suspicious artifacts and false-positive signals in mouse brain imaging. This study may open new avenues for contrast-enhanced MRI diagnosis and holds great promise for precision medicine.

Development of hollow ferrogadolinium nanonetworks for dual-modal MRI guided cancer chemotherapy.

The development of hollow ferrogadolinium nanonetworks has not been reported for nanomedicine application until now. In this study, we developed a hollow and porous ferrogadolinium nanonetwork structure using the one-pot solvothermal method. This nanoparticle could be simultaneously used as a T1 and T2 dual-modal magnetic resonance imaging (MRI) contrast agent. In addition, the hollow lumen and abundant pores of the nanonetworks maximized the loading capacity and conferred the nanoplatforms for suitable anticancer drug loading capacity. Using these nanonetworks, MRI and anticancer experiments were conducted in vitro and satisfactory dual-modal MRI and cancer chemotherapy results were obtained. Therefore, the nanonetworks with dual-modal MRI and drug loading abilities effectively complement the ferrogadolinium composites' library and hold great promise in nanomedicine for simultaneous cancer diagnosis and chemotherapy.

Albumin-based nanoparticles loaded with hydrophobic gadolinium chelates as T1–T2dual-mode contrast agents for accurate liver tumor imaging

Magnetic resonance contrast agents with T1-T2 dual mode contrast capability have attracted considerable interest because they offer complementary and synergistic diagnostic information, leading to high imaging sensitivity and accurate diagnosis. Here, we reported a facile strategy to construct albumin based nanoparticles loaded with hydrophobic gadolinium chelates by hydrophobic interaction for magnetic resonance imaging (MRI). We synthesized a glycyrrhetinic acid-containing Gd-DOTA derivative (GGD) and loaded GGD molecules into BSA nanoparticles to form GGD-BSA nanoparticles (GGD-BSA NPs). The large size and porous structure endow GGD-BSA NPs with geometrical confinement, which restricts the tumbling of GGD and the diffusion of surrounding water molecules. As a result, GGD-BSA NPs exhibit ultrahigh T1 and T2 relaxivities, which are approximately 8-fold higher than those of gadolinium-based clinical contrast agents at 0.5 T. Besides, due to the intrinsic properties of their components, GGD-BSA NPs show good biocompatibility in vitro and in vivo, which warrants their great potential in clinical translation. Furthermore, GGD-BSA NPs show remarkable sensitivity in noninvasive detection of liver tumors by self-confirmed T1-T2 dual-mode contrast-enhanced MRI. All of these merits make GGD-BSA NPs a potential candidate for fruitful biomedical and preclinical applications.

Synthesis of Ferromagnetic Fe0.6 Mn0.4 O Nanoflowers as a New Class of Magnetic Theranostic Platform for In Vivo T1 -T2 Dual-Mode Magnetic Resonance Imaging and Magnetic Hyperthermia Therapy.

Uniform wüstite Fe0.6 Mn0.4 O nanoflowers have been successfully developed as an innovative theranostic agent with T1 -T2 dual-mode magnetic resonance imaging (MRI), for diagnostic applications and therapeutic interventions via magnetic hyperthermia. Unlike their antiferromagnetic bulk counterpart, the obtained Fe0.6 Mn0.4 O nanoflowers show unique room-temperature ferromagnetic behavior, probably due to the presence of an exchange coupling effect. Combined with the flower-like morphology, ferromagnetic Fe0.6 Mn0.4 O nanoflowers are demonstrated to possess dual-modal MRI sensitivity, with longitudinal relaxivity r1 and transverse relaxivity r2 as high as 4.9 and 61.2 mm(-1) s(-1) [Fe]+[Mn], respectively. Further in vivo MRI carried out on the mouse orthotopic glioma model revealed gliomas are clearly delineated in both T1 - and T2 -weighted MR images, after administration of the Fe0.6 Mn0.4 O nanoflowers. In addition, the Fe0.6 Mn0.4 O nanoflowers also exhibit excellent magnetic induction heating effects. Both in vitro and in vivo magnetic hyperthermia experimentation has demonstrated that magnetic hyperthermia by using the innovative Fe0.6 Mn0.4 O nanoflowers can induce MCF-7 breast cancer cell apoptosis and a complete tumor regression without appreciable side effects. The results have demonstrated that the innovative Fe0.6 Mn0.4 O nanoflowers can be a new magnetic theranostic platform for in vivo T1 -T2 dual-mode MRI and magnetic thermotherapy, thereby achieving a one-stop diagnosis cum effective therapeutic modality in cancer management.

Redoxable heteronanocrystals functioning magnetic relaxation switch for activatable T1 and T2 dual-mode magnetic resonance imaging.

T1/T2 dual-mode magnetic resonance (MR) contrast agents (DMCAs) have gained much attention because of their ability to improve accuracy by providing two pieces of complementary information with one instrument. However, most of these agents are "always ON" systems that emit MR contrast regardless of their interaction with target cells or biomarkers, which may result in poor target-to-background ratios. Herein, we introduce a rationally designed magnetic relaxation switch (MGRS) for an activatable T1/T2 dual MR imaging system. Redox-responsive heteronanocrystals, consisting of a superparamagnetic Fe3O4 core and a paramagnetic Mn3O4 shell, are synthesized through seed-mediated growth and subsequently surface-modified with polysorbate 80. The Mn3O4 shell acts as both a protector of Fe3O4 in aqueous environments to attenuate T2 relaxation and as a redoxable switch that can be activated in intracellular reducing environments by glutathione. This simultaneously generates large amounts of magnetically decoupled Mn(2+) ions and allows Fe3O4 to interact with the water protons. This smart nanoplatform shows an appropriate hydrodynamic size for the EPR effect (10-100nm) and demonstrates biocompatibility. Efficient transitions of OFF/ON dual contrast effects are observed by invitro imaging and MR relaxivity measurements. The ability to use these materials as DMCAs is demonstrated via effective passive tumor targeting for T1- and T2-weighted MR imaging in tumor-bearing mice.

Novel Mn3[Co(CN)6]2@SiO2@Ag Core–Shell Nanocube: Enhanced Two‐Photon Fluorescence and Magnetic Resonance Dual‐Modal Imaging‐Guided Photothermal and Chemo‐therapy

The versatile Mn3[Co(CN)6]2@SiO2@Ag core-shell NCs are prepared by a simple coprecipitation method. Ag nanoparticles with an average diameter of 12 nm deposited on the surface of Mn3[Co(CN)6]2@SiO2 through S-Ag bonding are fabricated in ethanol solution by reducing silver nitrate (AgNO3 ) with NaBH4 . The NCs possess T1 -T2 dual-modal magnetic resonance imaging ability. The inner Prussian blue analogs (PBAs) Mn3[Co(CN)6]2 exhibit bright two-photon fluorescence (TPF) imaging when excited at 730 nm. Moreover, the TPF imaging intensity displays 1.85-fold enhancement after loading of Ag nanoparticles. Besides, the sample also has multicolor fluorescence imaging ability under 403, 488, and 543 nm single photon excitation. The as-synthesized Mn3[Co(CN)6]2@SiO2@Ag NCs show a DOX loading capacity of 600 mg g(-1) and exhibit an excellent ability of near-infrared (NIR)-responsive drug release and photothermal therapy (PTT) which is induced from the relative high absorbance in NIR region. The combined chemotherapy and PTT against cancer cells in vitro test shows high therapeutic efficiency. The multimodal treatment and imaging could lead to this material a potential multifunctional system for biomedical diagnosis and therapy.

Iron oxide/manganese oxide co-loaded hybrid nanogels as pH-responsive magnetic resonance contrast agents

This work described a proof of concept study of hybrid nanogel-based magnetic resonance contrast agents, SPIO@GCS/acryl/biotin@Mn-gel, abb. as SGM, for highly efficient, pH-responsive T1 and T2 dual-mode magnetic resonance imaging (MRI). SGM have been synthesized by assembling superparamagnetic iron oxide particles into polysaccharide nanoclusters, followed by in-situ reduction of the manganese species on the clusters and a final mild polymerization. The dual-mode SGM showed an interesting pH-responsiveness in in vitro MRI, with both T1 and T2 relaxivities turned “ON” in the acidic environment, along with an increase in the r1 and r2 relaxivity values by 1.7-fold (from 8.9 to 15.3 mM−1 S−1) and 4.9-fold (from 45.7 to 226 mM−1 S−1), due to desirable silencing and de-silencing effects. This interesting acidic-responsiveness was further verified in vivo with both significantly brightened signal of tumor tissue in T1-weighted MR images and a darkened signal in T2-weighted MR images 50 min post-injection of SGM. This smart hybrid nanogel may serve as a promising candidate for further studies of dual-mode (T1 and T2) contrast agents in MRI, due to its high stability, interesting pH-response mechanism and indicative imaging of tumors.