Magnetic Resonance Imaging Agents Research Articles

Local structural effects of Gd3+ ions incorporation in shell of nanostructured silica core – alumina rich shell microspheres

Non-crystalline nanostructured silica core – alumina rich shell microspheres, with Gd ions in the shell were obtained by sol-gel procedure following a synthesis route based on the Stöber method. The samples were characterized by DTA/TGA, XRD, SEM and TEM, EPR, solid-state NMR and XPS techniques. The effect of increasing Gd ions content on the local structure in alumina rich shell and at its interface with silica core was investigated. It was also found that increasing the concentration of the paramagnetic ions leads to a modification of the local magnetic field at sites of neighboring aluminum and silicon ions. Gadolinium ions are distributed in the aluminum sites from alumina rich shell. As result of increasing the gadolinium incorporation at the core-shell interface the diffusion of aluminum in the silica network, as well as the migration of the silicon in the alumina rich shell, are enhanced. Therefore, Si-O-Al bridges are formed at the interface, leading to stable non-crystalline structures, with Gd ions on the external layer of the shell, as proved by XPS, having potential application as contrast agents for magnetic resonance imaging (MRI).

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.

Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors.

Accurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer.Magneticresonance imaging (MRI)of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-linearaccelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of >90% of epithelial carcinomas. Herein, the authors compare targeted MRI of prostatespecificmembraneantigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA-targeting iron oxide nanoparticleswereprepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP-targeted MRI increased the proportion of tumor contrast-enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.

QUANTITATIVE ANALYSIS OF ELECTRICAL CURRENT EFFECT ON MAGNETIC RESONANCE IMAGE TISSUE INTENSITY

Recent studies in magnetic resonance imaging (MRI) aim to improve image quality while reducing scan time. Electrical current injection in the form of magnetic resonance electrical impedance tomography (MREIT) is believed to be affecting image quality and scan time thus can improve the possibility of becoming a non-chemical contrast agent in MRI. This study will observe and analyze the effect of electrical current injection on a phantom object to determine whether there is a different tissue image intensity. A thigh of lamb was used as a biological tissue phantom. The scan was performed on both T1and T2-weighted without and with an electrical current injection of 0.5 mA Electrical current injection decreased mean of tissue image intensity on T1-weighted images on both muscle (1759 vs 794) and bone (2752 vs 1550) (p<0.05). On the other hand, the electrical current increased mean of tissue image intensity on T2-weighted images on both muscle (303 vs 897) and bone (579 vs 1499) (p<0.05). There is also a difference in tissue image intensity on both T1 and T2-weighted images with and without electrical current injection on bone and muscle. The implication of this difference in image quality is a subject for further study.

Preparation of Functional Nanoparticles-Loaded Magnetic Carbon Nanohorn Nanocomposites towards Composite Treatment.

Combination therapy for cancer is expected for the synergetic effect of different treatments, and the development of promising carrier materials is demanded for new therapeutics. In this study, nanocomposites including functional nanoparticles (NPs) such as samarium oxide NP for radiotherapy and gadolinium oxide NP as a magnetic resonance imaging agent were synthesized and chemically combined with iron oxide NP-embedded or carbon dot-coating iron oxide NP-embedded carbon nanohorn carriers, where iron oxide NP is a hyperthermia reagent and carbon dot exerts effects on photodynamic/photothermal treatments. These nanocomposites exerted potential for delivery of anticancer drugs (doxorubicin, gemcitabine, and camptothecin) even after being coated with poly(ethylene glycol). The co-delivery of these anticancer drugs played better drug-release efficacy than the independent drug delivery, and the thermal and photothermal procedures enlarged the drug release. Thus, the prepared nanocomposites can be expected as materials to develop advanced medication for combination treatment.

Graphene quantum dots (GQDs) decorated Co-Zn ferrite: Structural, morphological, dielectric, and magnetic properties

GQDs/Co0.5Zn0.5Fe2O4 nanocomposite was synthesized using a facile sonication-assisted approach. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), elemental dispersive X-ray spectroscopy (EDX), impedance analyzer and vibrating sample magnetometer (VSM) were employed to characterize the synthesized samples. The XRD data confirmed the formation of GQDs, Co-Zn ferrite and GQDs/Co-Zn ferrite nanocomposite with no detectable impurity peaks. FTIR results identified the presence of GQDs in GQDs/Co-Zn ferrite nanocomposite. The morphological study revealed the decoration of spherical GQDs on the surface of Co-Zn ferrite. Complex impedance plane plots showed the contribution of the relaxation phenomenon associated with grain and grain boundaries in observed dielectric properties of the nanocomposite. The inclusion of GQDs led to the enhancement of the dielectric constant of the nanocomposite at low frequencies. GQDs/Co0.5Zn0.5Fe2O4 showed superparamagnetic properties which makes it a potential material to be used as a contrast agent in magnetic resonance imaging (MRI) applications.

A primer on contrast agents for magnetic resonance imaging of post‐procedural and follow‐up imaging of islet cell transplant

Abstractβ‐islet cell transplantation is a promising proposed treatment for type 1 diabetes mellitus (T1DM) which can provide more physiological glucose control when compared to exogenous insulin therapy and reverse secondary consequences of diabetes. Unfortunately, β‐islet cell transplantation is not a permanent solution for patients with T1DM as 85–90% of β‐islet recipients return to exogenous insulin treatment within 5 years of the transplant. Despite its lack of success, β‐islet cell transplantation still has potential for the treatment of T1DM and significant work has been done to non‐invasively quantify β‐islet cell concentrations in transplantation to better understand the mechanism of β‐islet cell rejection. While several imaging modalities have been utilized, magnetic resonance imaging (MRI) remains at the forefront of β‐islet cell imaging due to its high resolution and lack of radiation exposure to patients. Several MRI contrast agents have been explored for the imaging of β‐islet cells including superparamagnetic iron oxide nanoparticles (SPIONs), gadolinium‐based contrast agents (GBCA), manganese (II), fluorine‐19, and theranostic agents, with SPIONs being the most extensively studied. In this review, we provide an overview of the history, recent progress, and challenges of MRI in islet transplantation with a focus on the molecular imaging agents used.

Response of the Endogenous Antioxidant Defense System Induced in RAW 264.7 Macrophages upon Exposure to Dextran-Coated Iron Oxide Nanoparticles.

Presently, iron oxide nanoparticles are the only ones approved for clinical use as contrast agents in magnetic resonance imaging (MRI). Even though there is a high demand for these types of nanoparticles both for clinical use as well as for research, there are difficulties in obtaining stable nanoparticles with reproducible properties. In this context, in this study, we report the obtaining by an adapted coprecipitation method of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs). The morphology and structure of the dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) were determined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The TEM and SEM micrographs highlighted the obtaining of particles of nanometric size and spherical shape morphology. Furthermore, the high-resolution transmission electron microscopy (HRTEM), as well as selected area diffraction (SAED), revealed that the obtained samples presented the structure of cubic maghemite. In this study, we also explored the effects of the co-precipitation synthesized dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) on the redox status of macrophages. For cytotoxicity evaluation of these NPs, murine macrophages (RAW 264.7 cell line) were exposed to different concentrations of dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) corresponding to 0-500 μg Fe3+/mL and incubated for 24, 48, and 72 h. Intracellular iron uptake, changes in the oxidative stress parameters (reactive oxygen species production and malondialdehyde level), and the activity of antioxidant enzymes, as well as GSH concentration in cells, were evaluated after incubation with a lower (50 μg Fe3+/mL) and higher (500 μg Fe3+/mL) dose of NPs. The results indicated a significant decrease in RAW 264.7 cell viability after 72 h in the presence of NPs at concentrations above 25 μg Fe3+/mL. An important accumulation of NPs, dependent on dose and exposure time, was detected in macrophages, but it induced only a limited raise in the oxidative status. We showed here that the antioxidant capacity of RAW 264.7 macrophages was efficient in counteracting dextran-coated maghemite nanoparticles (ɤ-Fe2O3 NPs) toxicity even at higher doses.

Preparation and In Vitro Evaluation of a Gadolinium-Containing Vitamin E TPGS Micelle as a Potential Contrast Agent for MR Imaging

The application of many currently evaluated macromolecular contrast agents for magnetic resonance imaging (MRI) has been limited because of their bio-incompatibility and toxicity. The aim of this study is to synthesize and characterize a new micelle-based TPGS gadolinium chelate as a biocompatible MRI contrast agent for prolonged blood circulation time and good tumor imaging contrast. The TPGS-gadolinium conjugate was prepared through the conjugation between TPGS-SA and bifunctional L-NETA-Gd chelate. The conjugate was characterized with regard to molecular weight, critical micellar concentration and particle sizes, cellular uptake, and in vitro cell MRI. Distributions of the MRI contrast agent in various organs were determined via intravenous injection of the agent into mice bearing xenograft tumors. The successfully prepared TPGS-L-NETA-Gd micelle exhibited improved cellular uptake in HepG2 cells and xenografts and high in vivo safety. Distributions of TPGS-L-NETA-Gd in mice showed enhanced cellular uptake up to 2 h after the contrast agent injection. Its in vitro and in vivo properties make it a favorable macromolecular MRI contrast agent for future in vivo imaging.

An Ultrasound-Triggered Nanoplatform for Synergistic Sonodynamic-Nitric Oxide Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) has aroused intensive interest as a powerful alternative for cancer treatment in recent years due to its non-invasiveness and deep tissue penetration. However, the therapeutic effect of SDT alone is still limited by intrinsic hypoxia in solid tumors. Combined synergistic therapy strategies are highly desired for improving therapeutic efficiency. Herein, a rationally designed intelligent theranostic nanoplatform is developed for the enhancement of cancer treatment through synergistic SDT and nitric oxide (NO) therapy. This US-triggered nanoplatform is fabricated by integrating a sonosensitizer Rose Bengal (RB) and a NO donor (SNO) into manganese-doped hollow mesoporous silica nanoparticles (MH-SNO@RB). Impressively, the acidic and reducing tumor microenvironment accelerates the sustainable release of Mn ions from the framework, which facilitates the MH-SNO@RB to be used as a contrast agent for magnetic resonance imaging. More importantly, the reactive oxygen species (ROS) generated by RB and NO molecules released from SNO, which are simultaneously triggered by US, can react with each other to yield highly reactive peroxynitrite (ONOO-) ions for effective tumor inhibition both in vitro and in vivo. Furthermore, the nanoplatform demonstrates good hemocompatibility and histocompatibility. This study opens a new strategy for the full utilization of US and intelligent design avenues for high-performance cancer treatment.

Subtyping of hepatocellular adenomas using Gd-EOB-DTPA: a qualitative and quantitative analysis.

The goal of medical imaging is not only to identify the entity "hepatocellular adenoma," but to detect typical magnetic resonance (MR) patterns of the subtypes so that lesions with a higher malignant transformation rate could be differentiated from those that should just be controlled. To evaluate the differentiation between subtypes of hepatocellular adenomas using hepatobiliary specific contrast agent (Gd-EOB-DTPA) in MR imaging. A total of 11 patients with 39 lesions with histologically proven hepatocellular adenomas were evaluated. Of the, 34 were inflammatory hepatocellular adenomas (IHCA) and 5 were HNF1α adenomas. No β-catenin-mutated adenoma was found. In all patients, a standard protocol considering the guidelines of the international consensus conference of Gd-EOB-DTPA was performed in a 1.5-T scanner. Besides a qualitative analysis of all sequences, we measured the quantitative signal intensity (SI) ratio in all examinations. Qualitative analysis showed that best sequences for differentiation of HNF1α adenomas from IHCA were T1-weighted (T1W) precontrast (P = 0.03) and portalvenous phase (P < 0.0001) as well as arterial phase (P = 0.002). All adenomas were hypointense in hepatobiliary phase (15 min). The quantitative analyses of the SI ratio and of lesion-to-liver contrast (LLC) ratio show statistically significant differences in T1W precontrast (SI: P = 0.035; LLC: P = 0.049) and portalvenous phase (SI: P = 0.002; LLC: P = 0.002). Subtyping of hepatocellular adenomas using Gd-EOB-DTPA is possible due to qualitative and quantitative analyses regarding T1W precontrast and portalvenous phase. In addition, the SI ratio and liver-to-lesion contrast ratio in the arterial phase gave additional qualitative information for differentiation.

Contrast Agent Dose Reduction in MRI Utilizing a Generative Adversarial Network in an Exploratory Animal Study.

The aim of this study is to use virtual contrast enhancement to reduce the amount of hepatobiliary gadolinium-based contrast agent in magnetic resonance imaging with generative adversarial networks (GANs) in a large animal model. With 20 healthy Göttingen minipigs, a total of 120 magnetic resonance imaging examinations were performed on 6 different occasions, 50% with reduced (low-dose; 0.005 mmol/kg, gadoxetate) and 50% standard dose (normal-dose; 0.025 mmol/kg). These included arterial, portal venous, venous, and hepatobiliary contrast phases (20 minutes, 30 minutes). Because of incomplete examinations, one animal had to be excluded. Randomly, 3 of 19 animals were selected and withheld for validation (18 examinations). Subsequently, a GAN was trained for image-to-image conversion from low-dose to normal-dose (virtual normal-dose) with the remaining 16 animals (96 examinations). For validation, vascular and parenchymal contrast-to-noise ratio (CNR) was calculated using region of interest measurements of the abdominal aorta, inferior vena cava, portal vein, hepatic parenchyma, and autochthonous back muscles. In parallel, a visual Turing test was performed by presenting the normal-dose and virtual normal-dose data to 3 consultant radiologists, blinded for the type of examination. They had to decide whether they would consider both data sets as consistent in findings and which images were from the normal-dose study. The pooled dynamic phase vascular and parenchymal CNR increased significantly from low-dose to virtual normal-dose (pooled vascular: P < 0.0001, pooled parenchymal: P = 0.0002) and was found to be not significantly different between virtual normal-dose and normal-dose examinations (vascular CNR [mean ± SD]: low-dose 17.6 ± 6.0, virtual normal-dose 41.8 ± 9.7, and normal-dose 48.4 ± 12.2; parenchymal CNR [mean ± SD]: low-dose 20.2 ± 5.9, virtual normal-dose 28.3 ± 6.9, and normal-dose 29.5 ± 7.2). The pooled parenchymal CNR of the hepatobiliary contrast phases revealed a significant increase from the low-dose (22.8 ± 6.2) to the virtual normal-dose (33.2 ± 6.1; P < 0.0001) and normal-dose sequence (37.0 ± 9.1; P < 0.0001). In addition, there was no significant difference between the virtual normal-dose and normal-dose sequence. In the visual Turing test, on the median, the consultant radiologist reported that the sequences of the normal-dose and virtual normal-dose are consistent in findings in 100% of the examinations. Moreover, the consultants were able to identify the normal-dose series as such in a median 54.5% of the cases. In this feasibility study in healthy Göttingen minipigs, it could be shown that GAN-based virtual contrast enhancement can be used to recreate the image impression of normal-dose imaging in terms of CNR and subjective image similarity in both dynamic and hepatobiliary contrast phases from low-dose data with an 80% reduction in gadolinium-based contrast agent dose. Before clinical implementation, further studies with pathologies are needed to validate whether pathologies are correctly represented by the network.

Superparamagnetic Iron Oxide Nanoparticles (SPION): From Fundamentals to State-of-the-Art Innovative Applications for Cancer Therapy.

Despite significant advances in cancer therapy over the years, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With the advent of nanotechnologies, nanomedicine-based cancer therapy has been widely explored as a promising technology able to handle the requirements of the clinical sector. Superparamagnetic iron oxide nanoparticles (SPION) have been at the forefront of nanotechnology development since the mid-1990s, thanks to their former role as contrast agents for magnetic resonance imaging. Though their use as MRI probes has been discontinued due to an unfavorable cost/benefit ratio, several innovative applications as therapeutic tools have prompted a renewal of interest. The unique characteristics of SPION, i.e., their magnetic properties enabling specific response when submitted to high frequency (magnetic hyperthermia) or low frequency (magneto-mechanical therapy) alternating magnetic field, and their ability to generate reactive oxygen species (either intrinsically or when activated using various stimuli), make them particularly adapted for cancer therapy. This review provides a comprehensive description of the fundamental aspects of SPION formulation and highlights various recent approaches regarding in vivo applications in the field of cancer therapy.

A Multifunctional Integrated Metal-Free MRI Agent for Early Diagnosis of Oxidative Stress in a Mouse Model of Diabetic Cardiomyopathy.

Reactive oxygen species (ROS) are closely associated with the progression of diabetic cardiomyopathy (DCM) and can be regarded as one of its early biomarkers. Magnetic resonance imaging (MRI) is emerging as a powerful tool for the detection of cardiac abnormalities, but the sensitive and direct ROS-response MRI probe remains to be developed. This restricts the early diagnosis of DCM and prevents timely clinical interventions, resulting in serious and irreversible pathophysiological abnormalities. Herein, a novel ROS-response contrast-enhanced MRI nanoprobe (RCMN) is developed by multi-functionalizing fluorinated carbon nanosheets (FCNs) with multi-hydroxyl and 2,2,6,6-tetramethylpiperidin-1-oxyl groups. RCMNs capture ROS and then gather in the heart provisionally, which triggers MRI signal changes to realize the in vivo detection of ROS. In contrast to the clinical MRI agents, the cardiac abnormalities of disease mice is detected 8 weeks in advance with the assistance of RCMNs, which greatly advances the diagnostic window of DCM. To the best of the knowledge, this is the first ROS-response metal-free T2 -weighted MRI probe for the early diagnosis of DCM mice model. Furthermore, RCMNs can timely scavenge excessively produced ROS to alleviate oxidative stress.

Targeted treatment of triple-negative-breast cancer through pH-triggered tumour associated macrophages using smart theranostic nanoformulations

Triple-negative breast cancer (TNBC) represents 15–25 % of the new breast cancer cases diagnosed worldwide every year. TNBC is among the most aggressive and worst prognosis breast cancer, mainly because targeted therapies are not available. Herein, we developed a magnetic theranostic hybrid nanovehicle for targeted treatment of TNBC through pH-triggered tumour associated macrophages (TAMs) targeting. The lipid core of the nanovehicle was composed of a Carnaúba wax matrix that simultaneously incorporated iron oxide nanoparticles and doxorubicin (DOX) - a chemotherapeutic drug. These drug-loaded wax nanovehicles were modified with a combination of two functional and complementary molecules: (i) a mannose ligand (macrophage targeting) and (ii) an acid-sensitive sheddable polyethylene glycol (PEG) moiety (specificity). The TAMs targeting strategy relied on the mannose − mannose receptor recognition exclusively after acid-sensitive “shedding” of the PEG in the relatively low tumour microenvironment pH. The pH-induced targeting capability towards TAMs was confirmed in vitro in a J774A.1 macrophage cell line at different pH (7.4 and 6.5). Biocompatibility and efficacy of the final targeted formulations were demonstrated in vitro in the TNBC MDA-MB-231 cell line and in vivo in an M-Wnt tumour-bearing (TNBC) mouse model. A preferential accumulation of the DOX-loaded lipid nanovehicles in the tumours of M-Wnt-tumour bearing mice was observed, which resulted both on an efficient tumour growth inhibition and a significantly reduced off-target toxicity compared to free DOX. Additionally, the developed magnetic hybrid nanovehicles showed outstanding performances as T2-contrast agents in magnetic resonance imaging (r2 ≈ 400–600 mM−1·s−1) and as heat generating sources in magnetic hyperthermia (specific absorption rate, SAR ≈ 178 W·g−1Fe). These targeted magnetic hybrid nanovehicles emerge as a suitable theranostic option that responds to the urgent demand for more precise and personalized treatments, not only because they are able to offer localized imaging and therapeutic potential, but also because they allow to efficiently control the balance between safety and efficacy.

Curcumin Coated Ultra-Small Iron Oxide Nanoparticles as T1 Contrast Agents for Magnetic Resonance Imaging of Cancer Cells.

The application of nanotechnology in the molecular diagnosis and treatment of cancer is essential. This study aimed to investigate the influence of curcumin-coated ultra-small superparamagnetic iron oxide (USPIO) as a T1 contrast agent in Magnetic Resonance Imaging (MRI). In this experimental study, the influence of curcumin-coated USPIO (Fe3O4@C) on the diagnosis of the cancer cell line was investigated. After synthesis, characterization, and relaxation of Fe3O4@C, the contrast changes in T1-weight MRI to mouse colon carcinoma 26 cell line were evaluated in vitro. Fe3O4@C nanoparticles (NPs) are good at imaging; based on a relaxometry test, the r1 and r2 relaxivities of Dotarem were 3.139 and 0.603 mM-1s-1, respectively. Additionally, the r1 and r2 relaxivities of Fe3O4@C were 3.792 and 1.3 mM-1s-1, respectively, with the rate of 2.155 of r2/r1 NPs. The NPs can be identified as a positive contrast agent with a weight of T1 in MRI. The coresh-ell Fe3O4@C NPs can be effective in cancer treatment and diagnosis because of the therapeutic effects of curcumin and the properties of USPIO.

Hierarchical superparamagnetic metal-organic framework nanovectors as anti-inflammatory nanomedicines.

Among a plethora of drug nanocarriers, biocompatible nanoscale metal-organic frameworks (nanoMOFs) with a large surface area and an amphiphilic internal microenvironment have emerged as promising drug delivery platforms, mainly for cancer therapy. However, their application in biomedicine still suffers from shortcomings such as a limited chemical and/or colloidal stability and/or toxicity. Here, we report the design of a hierarchically porous nano-object (denoted as USPIO@MIL) combining a benchmark nanoMOF (that is, MIL-100(Fe)) and ultra-small superparamagnetic iron oxide (USPIO) nanoparticles (that is, maghemite) that is synthesized through a one-pot, cost-effective and environmentally friendly protocol. The synergistic coupling of the physico-chemical and functional properties of both nanoparticles confers to these nano-objects valuable features such as high colloidal stability, high biodegradability, low toxicity, high drug loading capacity as well as stimuli-responsive drug release and superparamagnetic properties. This bimodal MIL-100(Fe)/maghemite nanocarrier once loaded with anti-tumoral and anti-inflammatory drugs (doxorubicin and methotrexate) shows high anti-inflammatory and anti-tumoral activities. In addition, the USPIO@MIL nano-object exhibits excellent relaxometric properties and its applicability as an efficient contrast agent for magnetic resonance imaging is herein demonstrated. This highlights the high potential of the maghemite@MOF composite integrating the functions of imaging and therapy as a theranostic anti-inflammatory formulation.

A macrocyclic quinol-containing ligand enables high catalase activity even with a redox-inactive metal at the expense of the ability to mimic superoxide dismutase.

Previously, we found that linear quinol-containing ligands could allow manganese complexes to act as functional mimics of superoxide dismutase (SOD). The redox activity of the quinol enables even Zn(ii) complexes with these ligands to catalyze superoxide degradation. As we were investigating the abilities of manganese and iron complexes with 1,8-bis(2,5-dihydroxybenzyl)-1,4,8,11-tetraazacyclotetradecane (H4qp4) to act as redox-responsive contrast agents for magnetic resonance imaging (MRI), we found evidence that they could also catalyze the dismutation of H2O2. Here, we investigate the antioxidant behavior of Mn(ii), Fe(ii), and Zn(ii) complexes with H4qp4. Although the H4qp4 complexes are relatively poor mimetics of SOD, with only the manganese complex displaying above-baseline catalysis, all three display extremely potent catalase activity. The ability of the Zn(ii) complex to catalyze the degradation of H2O2 demonstrates that the use of a redox-active ligand can enable redox-inactive metals to catalyze the decomposition of reactive oxygen species (ROS) besides superoxide. The results also demonstrate that the ligand framework can tune antioxidant activity towards specific ROS.

Emergence of magnetic nanoparticles in photothermal and ferroptotic therapies.

With their distinctive physicochemical features, nanoparticles have gained recognition as effective multifunctional tools for biomedical applications, with designs and compositions tailored for specific uses. Notably, magnetic nanoparticles stand out as first-in-class examples of multiple modalities provided by the iron-based composition. They have long been exploited as contrast agents for magnetic resonance imaging (MRI) or as anti-cancer agents generating therapeutic hyperthermia through high-frequency magnetic field application, known as magnetic hyperthermia (MHT). This review focuses on two more recent applications in oncology using iron-based nanomaterials: photothermal therapy (PTT) and ferroptosis. In PTT, the iron oxide core responds to a near-infrared (NIR) excitation and generates heat in its surrounding area, rivaling the efficiency of plasmonic gold-standard nanoparticles. This opens up the possibility of a dual MHT + PTT approach using a single nanomaterial. Moreover, the iron composition of magnetic nanoparticles can be harnessed as a chemotherapeutic asset. Degradation in the intracellular environment triggers the release of iron ions, which can stimulate the production of reactive oxygen species (ROS) and induce cancer cell death through ferroptosis. Consequently, this review emphasizes these emerging physical and chemical approaches for anti-cancer therapy facilitated by magnetic nanoparticles, combining all-in-one functionalities.

A robust MRI contrast agent for specific display of the interstitial stream.

Experimental and clinical studies have reported phenomena of long-range fluid flow in interstitial space. However, its behaviours and functions are yet to be addressed. The imaging of the interstitial stream in vivo can clarify its transportation route and allow further understanding of physiological mechanisms and clinical relevance. Here to illustrate the route of the interstitial stream leading to the kidney, we design and synthesize a magnetic resonance imaging (MRI) contrast agent PAA-g-(DTPA-gadolinium). This MRI agent has a high longitudinal relaxivity for higher MRI contrast and large size to avoid leakage across the interstitial space. Using dynamic contrast enhanced MRI, histochemical staining, and trace element analysis of gadolinium, we track the nano-scale PAA-g-(DTPA-gadolinium) transported in the interstitial stream. The agent can be applied for a wide range of imaging and analysis of tissues and organs, thereby enabling advances in the fields of physiology, pathology, and pharmacology.