Magnetic Resonance Imaging Contrast Agents Research Articles

A case of severe anaphylactic reaction after administration of diagnostic-dose ferumoxytol in a pediatric patient

We describe a case of anaphylaxis during administration of intravenous (IV) ferumoxytol as a magnetic resonance imaging (MRI) contrast agent in a 4-year-old patient with complicated past medical history including YARS genetic mutation with resultant liver failure and deceased donor liver transplantation, stage IV chronic kidney disease (CKD), and hypertension. The patient was noted to have labored breathing 4 min after initiation of ferumoxytol infusion and was subsequently rapidly intubated and returned to the intensive care unit (ICU) for monitoring. Anaphylactic reactions to therapeutic doses of ferumoxytol led to issuance of a black box warning by the FDA in 2015. Adverse reactions to lower-dose ferumoxytol used in diagnostic imaging, however, are rare and there has been a paucity of documented anaphylactic reactions in the literature.

Intramolecular Hydrogen Bonding Based CEST MRI Contrast Agents As an Emerging Design Strategy: A Mini-Review.

Intramolecular hydrogen bonding-based chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) contrast agents represent an innovative design strategy aiming to overcome limitations in diamagnetic CEST (diaCEST) MRI contrast agent specificity and also those associated with traditional metal-based MRI contrast agents. Ward and Balaban's proposal of small diamagnetic compounds marked a paradigm shift in contrast-based radiologic research, inspiring extensive investigations since 2000. These contrast agents leverage labile hydrogen bonds, serving as chemical exchange sites to induce saturation of water. The selective manipulation of radiofrequency (RF) allows for optimized signal contrast in soft tissue, with a significant signal amplification even at low probe concentrations, mitigating concerns about dose-dependent toxicities. This mini-review delves into the evolution of CEST MRI, its classification, and the strategic design principles of synthetic small molecules containing intramolecular hydrogen bonds. With a focus on applications and potential clinical relevance, the authors highlight the promising role of intramolecular hydrogen bonding-based CEST MRI in diverse medical contexts, especially renal imaging and pH mapping, paving the way for enhanced molecular imaging capabilities. Ongoing research endeavors aim to further optimize and expand the utility of these contrast agents, underscoring their transformative potential in clinical diagnostics and imaging.

Black TiO2-based nanoparticles as Toll-like receptor stimulator delivery system for enhanced photothermal-immunotherapy of pancreatic cancer

BackgroundThe tumor-specific immune responses, essential for removing residual lesions and preventing tumor metastases, can be stimulated by tumor-associated antigens (TAAs) released following photothermal therapy (PTT). However, due to the immunosuppressed microenvironment of pancreatic ductal adenocarcinoma (PDAC), the TAAs released by PTT are difficult to induce an effective immune response. In this work, we prepared the mesoporous silica (mSiO2) coated black titanium dioxide (bTiO2) photothermal nanoparticles (NPs) for enhanced photothermal-immunotherapy toward PDAC, in which resiquimod (R848) was loaded and DOTA-Gd was conjugated. The NPs are specified as bTiO2@mSiO2@Gd/R848 and abbreviated to NPs/R848. R848 as a kind of Toll-like receptor 7/8 agonist can remodel the tumor microenvironment (TME) in PDAC and induce a strong immune response. Furthermore, DOTA-Gd serves as a magnetic resonance imaging (MRI) contrast agent to improve the T1-weighted MRI performance of the NPs.ResultsIn vitro results of this study show that NPs/R848 could thermally ablate tumor cells and efficiently trigger dendritic cell (DC) maturation. The results of in vivo investigations demonstrate that the combined use of photothermal-immunotherapy exhibits a significant inhibitory effect on tumor growth. Besides, it promoted maturation of DCs and enhanced infiltration of CD8 + , CD4 + T cells to improve the TME in PDAC.ConclusionsOur study anticipates that by encouraging the maturation of DCs, this strategy will improve the TME and enable the successful photothermal-immunotherapy of PDAC.

Noninvasive platelet membrane-coated Fe3O4 nanoparticles identify vulnerable atherosclerotic plaques.

Vulnerable atherosclerotic plaques serve as the primary pathological basis for fatal cardiovascular and cerebrovascular diseases. The precise identification and treatment of these vulnerable plaques hold paramount clinical importance in mitigating the incidence of myocardial infarction and stroke. Nevertheless, the identification of vulnerable plaques within the diffuse atherosclerotic plaques dispersed throughout the systemic circulation continues to pose a substantial challenge in clinical practice. Double emulsion solvent evaporation method, specifically the water-in-oil-in-water (W/O/W) technique, was employed to fabricate Fe3O4-based poly (lactic-co-glycolic acid) (PLGA) nanoparticles (Fe3O4@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound-assisted encapsulation onto the surface of Fe3O4@PLGA, resulting in the formation of PM-coated Fe3O4 nanoparticles (PM/Fe3O4@PLGA). Characterization of PM/Fe3O4@PLGA involved the use of dynamic light scattering, transmission electron microscopy, western blotting, and magnetic resonance imaging (MRI). A model of atherosclerotic vulnerable plaques was constructed by carotid artery coarctation and a high-fat diet fed to ApoE-/- (Apolipoprotein E knockout) mice. Immunofluorescence and MRI techniques were employed to verify the functionality of PM/Fe3O4@PLGA. In this study, we initially synthesized Fe3O4@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the Fe3O4@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/Fe3O4@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/Fe3O4@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/Fe3O4@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/Fe3O4@PLGA has not demonstrated significant organ toxicity or inflammatory response in the bloodstream. In this study, we successfully developed a platelet-membrane-coated nanoparticle system for the targeted delivery of Fe3O4@PLGA to vulnerable atherosclerotic plaques. This innovative system allows for the visualization of vulnerable plaques using MRI, thereby demonstrating its potential for enhancing the clinical diagnosis of vulnerable atherosclerotic plaques.

Towards medical imaging of drug photoactivation: Development of light responsive magnetic resonance imaging and chemical exchange saturation transfer contrast agents

AbstractIn recent years, the use of light to selectively and precisely activate drugs has been developed along the fundamental concepts of photopharmacology. One of the key methods in this field relies on transiently silencing the drug activity with photocleavable protecting groups (PPGs). To effectively utilize light‐activated drugs in future medical applications, physicians will require a reliable method to assess whether light penetrates deep enough into the tissues to activate the photoresponsive theragnostic agents. Here, we describe the development and evaluation of magnetic resonance (MR) imaging agents that allow for the detection of light penetration and drug activation in the tissues using non‐invasive whole‐body magnetic resonance imaging (MRI) and chemical exchange saturation transfer (CEST)‐MRI modalities. The approach relies on the use of PPG‐protected MR contrast agents, which upon irradiation with light change their imaging signal. A Gadolinium(III)‐based MRI contrast agent is presented that undergoes a significant change in relaxivity (25%) upon uncaging, providing a reliable indicator of light‐induced cargo release. Additionally, we introduce the first light‐responsive CEST‐MRI imaging agent, enabling positive signal enhancement (off‐to‐on) upon light activation, offering a novel approach to visualize the activation of photoactive agents in living tissues. This research provides a proof‐of‐principle for the non‐invasive, whole‐body imaging of light penetration and drug activation with high temporal resolution characteristic of MR methods.

Microglial activation-sensitive gadolinium complex as a potential MRI contrast agent for Alzheimer’s disease diagnosis

Numerous studies have developed gadolinium (Gd)-based contrast agents (GBCAs) for in-vivo magnetic resonance imaging (MRI) with the aim of diagnosing Alzheimer’s disease (AD). Nevertheless, GBCAs that are capable of identifying microglial activation, a critical early indicator of AD pathology, for in-vivo diagnosis remain scarce. In response to this, we synthesized a novel GBCA, Gd-DO3A-Va, designed specifically to detect microglial activation using MRI. This innovative GBCA, which was conjugated with vanillic acid, demonstrated a high selectivity for microglial activation by targeting Toll-like receptor 4 (TLR4). The use of Gd-DO3A-Va in in-vivo imaging successfully highlighted microglial activation in a transgenic AD mouse model. In particular, the use of Gd-DO3A-Va for contrast-enhanced T1-weighted MRI enabled the detection of microglial activation within the hippocampus and cortex, regions notably affected by AD. The observed enhancements in the MR contrast correlated well with immunohistological evidence of microglial activation. Consequently, Gd-DO3A-Va represents a highly promising GBCA for the identification of microglial activation, providing a novel pathway for the molecular diagnosis of AD.

Dynamic monitoring soft tissue healing via visualized Gd-crosslinked double network MRI microspheres

By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.

Injectable Thermogelling Nanostructured Ink as Simultaneous Optical and Magnetic Resonance Imaging Contrast Agent for Image-Guided Surgery.

The development of efficient and biocompatible contrast agents is particularly urgent for modern clinical surgery. Nanostructured materials raised great interest as contrast agents for different imaging techniques, for which essential features are high contrasts, and in the case of precise clinical surgery, minimization of the signal spatial dispersion when embedded in biological tissues. This study deals with the development of a multimodal contrast agent based on an injectable hydrogel nanocomposite containing a lanthanide-activated layered double hydroxide coupled to a biocompatible dye (indocyanine green), emitting in the first biological window. This novel nanostructured thermogelling hydrogel behaves as an efficient tissue marker for optical and magnetic resonance imaging because the particular formulation strongly limits its spatial diffusion in biological tissue by exploiting a simple injection. The synergistic combination of these properties permits to employ the hydrogel ink simultaneously for both optical and magnetic resonance imaging, easy monitoring of the biological target, and, at the same time, increasing the spatial resolution during a clinical surgery. The biocompatibility and excellent performance as contrast agents are very promising for possible use in image-guided surgery, which is currently one of the most challenging topics in clinical research.

Structural Defect-Enabled Magnetic Neutrality Nanoprobes for Ultra-High-Field Magnetic Resonance Imaging of Isolated Tumor Cells in Vivo.

The identification of metastasis "seeds," isolated tumor cells (ITCs), is of paramount importance for the prognosis and tailored treatment of metastatic diseases. The conventional approach to clinical ITCs diagnosis through invasive biopsies is encumbered by the inherent risks of overdiagnosis and overtreatment. This underscores the pressing need for noninvasive ITCs detection methods that provide histopathological-level insights. Recent advancements in ultra-high-field (UHF) magnetic resonance imaging (MRI) have ignited hope for the revelation of minute lesions, including the elusive ITCs. Nevertheless, currently available MRI contrast agents are susceptible to magnetization-induced strong T2-decaying effects under UHF conditions, which compromises T1 MRI capability and further impedes the precise imaging of small lesions. Herein, this study reports a structural defect-enabled magnetic neutrality nanoprobe (MNN) distinguished by its paramagnetic properties featuring an exceptionally low magnetic susceptibility through atomic modulation, rendering it almost nonmagnetic. This unique characteristic effectively mitigates T2-decaying effect while concurrently enhancing UHF T1 contrast. Under 9 T MRI, the MNN demonstrates an unprecedentedly low r2/r1 value (≈1.06), enabling noninvasive visualization of ITCs with an exceptional detection threshold of ≈0.16mm. These high-performance MNNs unveil the domain of hitherto undetectable minute lesions, representing a significant advancement in UHF-MRI for diagnostic purposes and fostering comprehensive metastasis research.

Evaluation of the biodistribution and preliminary safety profile of a novel brain-targeted manganese dioxide-based nanotheranostic system for Alzheimer’s disease

A novel brain-targeted and reactive oxygen species-activatable manganese dioxide containing nanoparticle system functionalized with anti-amyloid-β antibody (named aAβ-BTRA-NC) developed by our group has shown great promise as a highly selective magnetic resonance imaging (MRI) contrast agent for early detection and multitargeted disease-modifying treatment of Alzheimer’s disease (AD). To further evaluate the suitability of the formulation for future clinical application, we investigated the safety, biodistribution, and pharmacokinetic profile of aAβ-BTRA-NC in a transgenic TgCRND8 mouse AD model, wild type (WT) littermate, and CD-1 mice. Dose-ascending studies demonstrated that aAβ-BTRA-NC was well-tolerated by the animals up to 300 μmol Mn/kg body weight [b.w.], 3 times the efficacious dose for early AD detection without apparent adverse effects; Histopathological, hematological, and biochemical analyses indicated that a single dose of aAβ-BTRA-NC did not cause any toxicity in major organs. Immunotoxicity data showed that aAβ-BTRA-NC was safer than commercially available gadolinium-based MRI contrast agents at an equivalent dose of 100 μmol/kg b.w. of metal ions. Intravenously administered aAβ-BTRA-NC was taken up by main organs with the order of liver, kidneys, intestines, spleen, followed by other organs, and cleared after one day to one week post injection. Pharmacokinetic analysis indicated that the plasma concentration profile of aAβ-BTRA-NC followed a 2-compartmental model with faster clearance in the AD mice than in the WT mice. The results suggest that aAβ-BTRA-NC exhibits a strong safety profile as a nanotheranostic agent which warrants more robust preclinical development for future clinical applications.

A responsive nanoplatform with molecular and structural imaging capacity for assisting accurate diagnosis of early rheumatoid arthritis

Accurate early diagnosis of rheumatoid arthritis (RA) and prompt implementation of appropriate treatment approaches are crucial. In the clinic, magnetic resonance imaging (MRI) has been recommended for implementation to aid in the precise and early diagnosis of RA. However, they are still limited by issues regarding specificity and their ability to capture comprehensive information about the pathological features. Herein, a responsive multifunctional nanoplatform with targeting capabilities (hMnO2-IR@BSA-PEG-FA) is constructed through integrating a RA microenvironment-responsive MRI contrast agent with activatable near-infrared (NIR) fluorescence imaging, aiming to simultaneously acquire comprehensive pathological features of RA from both structural and molecular imaging perspectives. Moreover, taking advantage of its targeting function to synovial microphages, hMnO2-IR@BSA-PEG-FA demonstrated a remarkable capability to accumulate effectively at the synovial tissue. Additionally, hMnO2 responded to the mild acidity and reactive oxygen species (ROS) in the RA microenvironment, leading to the controlled release of Mn2+ ions and IR780, which separately caused special MRI contrast enhancement of synovial tissues and sensitively demonstrated the presence of ROS and weakly acid microenvironment by NIR imaging. Consequently, hMnO2-IR@BSA-PEG-FA is expected to serve as a promising nanoplatform, offering valuable assistance in the precise diagnosis of early-stage RA by specially providing comprehensive information about the pathological features.

Dual-targeted delivery of temozolomide by multi-responsive nanoplatform via tumor microenvironment modulation for overcoming drug resistance to treat glioblastoma.

Glioblastoma (GBM) is the most aggressive primary brain tumor with low survival rate. Currently, temozolomide (TMZ) is the first-line drug for GBM treatment of which efficacy is unfortunately hindered by short circulation time and drug resistance associated to hypoxia and redox tumor microenvironment. Herein, a dual-targeted and multi-responsive nanoplatform is developed by loading TMZ in hollow manganese dioxide nanoparticles functionalized by polydopamine and targeting ligands RAP12 for photothermal and receptor-mediated dual-targeted delivery, respectively. After accumulated in GBM tumor site, the nanoplatform could respond to tumor microenvironment and simultaneously release manganese ion (Mn2+), oxygen (O2) and TMZ. The hypoxia alleviation via O2 production, the redox balance disruption via glutathione consumption and the reactive oxygen species generation, together would down-regulate the expression of O6-methylguanine-DNA methyltransferase under TMZ medication, which is considered as the key to drug resistance. These strategies could synergistically alleviate hypoxia microenvironment and overcome TMZ resistance, further enhancing the anti-tumor effect of chemotherapy/chemodynamic therapy against GBM. Additionally, the released Mn2+ could also be utilized as a magnetic resonance imaging contrast agent for monitoring treatment efficiency. Our study demonstrated that this nanoplatform provides an alternative approach to the challenges including low delivery efficiency and drug resistance of chemotherapeutics, which eventually appears to be a potential avenue in GBM treatment.

Thermal plasma synthesized Mn3O4 nanoparticles as T1 and T2 MRI contrast agents

In Magnetic Resonance Imaging (MRI), manganese oxides are predominantly used as contrast agents (CAs) to enhance contrast of T1–weighted acquisitions. In this work, Mn3O4 nanomaterials were synthesized by high temperature thermal plasma route and thoroughly characterized by structural, microscopic and biocompatibility investigations. The nanoparticles so obtained display both T1 and T2 MRI contrast properties. This was attributed to the fact that the nanomaterials synthesized by thermal plasma route possess higher saturation magnetization than those synthesized by various chemical methods. The presence of oxygen vacancies and relatively large size of the synthesized nanoparticles can also be regarded as other two reasons behind attainment of T1-T2 dual contrast. Thermal plasma synthesized nanomaterials have never been earlier demonstrated as MRI CAs. Moreover, this is the first report presenting detailed characterization of the thermal plasma synthesized Mn3O4. The microstructure of the synthesized Mn3O4 nanoparticles was observed to be spherical in shape. The biocompatibility of the developed nanosystem was established by cell viability analysis. Finally, the efficiency of the agent for T1–T2 contrast enhancement was confirmed through MRI experiments. This work lays the foundation of research on a new class of MRI CAs synthesized by thermal plasma.

Green synthesis and optimization of iron oxide nanoparticles as MRI contrast agent

Iron nanoparticles (FeNPs) derived from herbal plants are being explored as potential magnetic resonance imaging (MRI) contrast agents due to their biocompatibility and ability to perform targeted drug delivery. For the first time, the usage of various novel combinations of leaf extracts such as those of Azadirachta indica and Piper betle and extracts of two other Ayurvedic herbs – namely, Asparagus racemosus and Symplocos – was attempted for eco-friendly green synthesis of FeNPs. The nanoparticles were coated onto nanofibers made from a banana pseudo-stem (FENPs-NF) to enhance their biocompatibility. The synthesis process was optimized using response surface methodology, and techniques such as ultraviolet–visible (UV–Vis) spectroscopy, vibrating-sample magnetometry, atomic absorption spectroscopy (AAS), field-emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX) and Fourier transform infrared spectroscopy (FT-IR) were used for characterization. Hemolytic and immune cell assays, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and MRI analysis were carried out. A peak at 325 nm observed in UV–Vis spectroscopy, AAS, FE-SEM, EDX and FT-IR proved the presence of FeNPs. Hemolytic and immune cell assays indicated biocompatibility, and the MTT assay (MCF-7) showed inhibition at 250 μg/ml. FeNPs and FeNPs-NF showed a good signal loss in MRI analysis at 1.5 T, proving their contrast agent nature. Thus, FeNPs synthesized from herbal plant sources may open a new door for potential application in the biomedical field as a chemical-free and biocompatible MRI contrast agent.

Chiral Pyclen-Based Heptadentate Chelates as Highly Stable MRI Contrast Agents.

In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.

Evolving Characteristics of Gadolinium-Based Contrast Agents for MR Imaging: A Systematic Review of the Importance of Relaxivity.

Gadolinium-based contrast agents (GBCAs) are widely and routinely used to enhance the diagnostic performance of magnetic resonance imaging and magnetic resonance angiography examinations. T1 relaxivity (r1) is the measure of their ability to increase signal intensity in tissues and blood on T1-weighted images at a given dose. Pharmaceutical companies have invested in the design and development of GBCAs with higher and higher T1 relaxivity values, and "high relaxivity" is a claim frequently used to promote GBCAs, with no clear definition of what "high relaxivity" means, or general concurrence about its clinical benefit. To understand whether higher relaxivity values translate into a material clinical benefit, well-designed, and properly powered clinical studies are necessary, while mere in vitro measurements may be misleading. This systematic review of relevant peer-reviewed literature provides high-quality clinical evidence showing that a difference in relaxivity of at least 40% between two GBCAs results in superior diagnostic efficacy for the higher-relaxivity agent when this is used at the same equimolar gadolinium dose as the lower-relaxivity agent, or similar imaging performance when used at a lower dose. Either outcome clearly implies a relevant clinical benefit. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Magnetic Field-Optimized Paramagnetic Nanoprobe for T2/T1 Switchable Histopathological-Level MRI.

Traditional magnetic resonance imaging (MRI) contrast agents (CAs) are a type of "always on" system that accelerates proton relaxation regardless of their enrichment region. This "always on" feature leads to a decrease in signal differences between lesions and normal tissues, hampering their applications in accurate and early diagnosis. Herein, we report a strategy to fabricate glutathione (GSH)-responsive one-dimensional (1-D) manganese oxide nanoparticles (MONPs) with improved T2 relaxivities and achieve effective T2/T1 switchable MRI imaging of tumors. Compared to traditional contrast agents with high saturation magnetization to enhance T2 relaxivities, 1-D MONPs with weak Ms effectively increase the inhomogeneity of the local magnetic field and exhibit obvious T2 contrast. The inhomogeneity of the local magnetic field of 1-D MONPs is highly dependent on their number of primary particles and surface roughness according to Landau-Lifshitz-Gilbert simulations and thus eventually determines their T2 relaxivities. Furthermore, the GSH responsiveness ensures 1-D MONPs with sensitive switching from the T2 to T1 mode in vitro and subcutaneous tumors to clearly delineate the boundary of glioma and metastasis margins, achieving precise histopathological-level MRI. This study provides a strategy to improve T2 relaxivity of magnetic nanoparticles and construct switchable MRI CAs, offering high tumor-to-normal tissue contrast signal for early and accurate diagnosis.

Nanotechnology's Applications and Potential in Various Fields.

Since ancient times, several sorts of nanoparticles have been employed in the quickly expanding field of nanotechnology. These features include size, shape, and chemical as well as physical properties.Because of their small size and huge surface area, carbon-based nanoparticles, including fullerenes, carbon nanotubes, graphene, graphene oxide, and carbon-based quantum dots, have attracted a lot of attention in a variety of sectors, including biomedical applications. Lipid bilayers form the spherical vesicles known as liposomes. Magnetic resonance imaging (MRI) contrast agents are iron oxide nanoparticles. These materials are perfect for drug and delivery of genes, bioimaging, and bone repair because of their remarkable mechanical, electrical, visual, and chemical properties. However, concerns about potential asbestos-related diseases have arisen due to their length-to-width aspect ratio. Ceramic nanoparticles, on the other hand, are a common material in daily life and play a crucial role in bone repair, multiscale hybridisation, and aerospace structures. These nanoparticles can enhance osseointegration and bone development by mimicking the nanocomposition and nanoscale characteristics of bone tissue and enhance osteoconductive and osteoinductive capacities. Ceramic nanoparticles, however, have the potential to generate oxidative stress, which can result in irritation of the reticuloendothelial system, cytotoxicity to the heart, liver, and lungs, as well as toxicity to the cells that are attached. Additionally, oxidative stress, cell damage, and genotoxicity might result from the generation of free radicals by ceramic nanoparticles. Metal nanoparticles exhibit linear optical properties similar to molecular systems but arise from a different physical process. Semiconductor nanocrystals (NCs) are made from various compounds, such as silicon and germanium. Polyandry nanoparticles are particles approximately 10 and 10000 nanometers (nm) in size that can contain active substances. They have applications in vaccine delivery, gene therapy, and polymer nanoparticles (nanomedicine) for therapeutic applications.

A self-assembled theranostic nanoplatform for efficient tumor sonodynamic-gas therapy

The powerful antioxidant system in tumor tissues limits the efficacy of sonodynamic therapy (SDT) by reducing the availability of the produced reactive oxygen species (ROS). To address this problem, a pH/ultrasound (US) responsive theranostic nanoplatform is elaborately constructed by self-assembly of nitrogen-doped graphene quantum dots (NGQDs), benzothiazole sulfinate (BTS), Gd3+ ions and poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG). The NGQD component with excellent sonodynamic activity wrapped in the resulting Gd-NGQDs/BTS@PLGA-PEG can efficaciously respond to ultrasonic irradiation and cause abundant ROS generation. Importantly, in response to acidic tumor microenvironment, the loaded BTS sustainably releases SO2, which induces the increase of intracellular •O2− level by inhibiting superoxide dismutase activity and further promotes the enrichment of ROS by reducing intracellular glutathione level and suppressing glutathione peroxidase 4 activity. The well-designed SO2 gas therapy-enhanced SDT strategy leads to high oxidative stress in tumor cells and effective inhibition of the growth of bilateral tumors with only a single intravenous injection of the nanomedicine and a subsequent single US irradiation. Gd-NGQDs/BTS@PLGA-PEG can also be employed as a good T1-weighted magnetic resonance imaging contrast agent to guide tumor therapy. This innovative therapeutic strategy developed in our contribution may provide a new paradigm for the exploration of deep tumor therapy.

Ultra-small Janus nanoparticle-induced activation of ferroptosis for synergistic tumor immunotherapy

Ferroptosis induced by lipid peroxide (LPO) accumulation is an effective cell death pathway for cancer therapy. However, how to effectively induce ferroptosis at tumor sites and improve its therapeutic effectiveness remains challenging. Here, MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex with tumor-specific targeting and TME response is constructed to overcome immunosuppressive tumor microenvironment (TME) to potentiate the curative effect of ferroptosis by coupling the immune checkpoint indoleamine 2,3-dioxygenase (IDO) inhibitor, NLG919, and hyaluronic acid (HA) to novel ultra-small MnFe2O4@NaGdF4 (MG) nanoparticles with a Janus structure. Firstly, tumor site-precise delivery of MG and NLG919 is achieved with HA targeting. Secondly, MG acts as a magnetic resonance imaging contrast agent, which not only has a good photothermal effect to realize tumor photothermal therapy, but also depletes glutathione and catalyzes the production of reactive oxygen species from endogenous H2O2, which effectively promotes the accumulation of LPO and inhibits the expression of glutathione peroxidase 4, achieving enhanced ferroptosis. Thirdly, NLG919 inhibits the differentiation of Tregs by blocking the tryptophan/kynurenine immune escape pathway, thereby reversing immunosuppressive TME together with the Mn2+-activated cGAS-STING pathway. This work contributes new perspectives for the development of novel ultra-small Janus nanoparticles to reshape immunosuppressive TME and ferroptosis activation. Statement of significanceThe Janus structured MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex was synthesized, which can realize the precise delivery of T1/T2 contrast agents MnFe2O4@NaGdF4 (MG) and NLG919 at the tumor site under the ultra-small Janus structural characteristics and targeted molecule HA. The production of ROS, consumption of GSH, and photothermal properties of MGNH make it possible for CDT/PTT activated ferroptosis, and synergistically disrupt and reprogram tumor growth and immunosuppressive tumor microenvironment with NLG919 and Mn2+-mediated activation of cGAS-STING pathway, achieving CDT/PTT/immunotherapy activated by ferroptosis. Meanwhile, ultra-small structural properties of MGNH facilitate subsequent metabolic clearance by the body, allowing for the minimization of potential biotoxicity associated with its prolonged retention.