Noninvasive Diagnosis of Kidney Dysfunction Using a Small-Molecule Manganese-Based Magnetic Resonance Imaging Probe.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a promising approach for the diagnosis of kidney diseases. However, safety concerns, including nephrogenic systemic fibrosis, limit the administration of gadolinium (Gd)-based contrast agents (GBCAs) in patients who suffer from renal impairment. Meanwhile, nanomaterials meet biosafety concerns because of their long-term retention in the body. Herein, we propose a small-molecule manganese-based imaging probe Mn-PhDTA as an alternative to GBCAs to assess renal insufficiency for the first time. Mn-PhDTA was synthesized via a simple three-step reaction with a total yield of up to 33.6%, and a gram-scale synthesis can be realized. Mn-PhDTA has an r1 relaxivity of 2.72 mM-1 s-1 at 3.0 T and superior kinetic inertness over Gd-DTPA and Mn-EDTA with a dissociation time of 60 min in the presence of excess Zn2+. In vivo and in vitro experiments demonstrate their good stability and biocompatibility. In the unilateral ureteral obstruction rats, Mn-PhDTA provided significant MR signal enhancement, enabled distinguishing structure changes between the normal and damaged kidneys, and evaluated the renal function at different injured stages. Mn-PhDTA could act as a potential MRI contrast agent candidate for the replacement of GBCAs in the early detection of kidney dysfunction and analysis of kidney disease progression.

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 25.8 nm), 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 0.1 mm 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.

Engineering Persistent Luminescence Nanoparticles for Biological Applications: From Biosensing/Bioimaging to Theranostics.

Persistent luminescence nanoparticles (PLNPs) are unique optical materials emitting long-lasting luminescence after ceasing excitation. Such a unique optical feature allows luminescence detection without constant external illumination to avoid the interferences of autofluorescence and scattering light from biological fluids and tissues. Besides, near-infrared (NIR) PLNPs have advantages of deep penetration and the reactivation of the persistent luminescence (PL) by red or NIR light. These features make the application of NIR-emitting PLNPs in long-term bioimaging no longer limited by the lifetime of PL. To take full advantage of PLNPs for biological applications, the versatile strategies for bridging PLNPs and biological system become increasingly significant for the design of PLNPs-based nanoprobes. In this Account, we summarize our systematic achievements in the biological applications of PLNPs from biosensing/bioimaging to theranostics with emphasizing the engineering strategies for fabricating specific PLNPs-based nanoprobes. We take surface engineering and manipulating energy transfer as the major principles to design various PLNPs-based nanoprobes based on the nature of interactions between nanoprobes and targets. We have developed target-induced formation or interruption of fluorescence resonance energy transfer systems for autofluorescence-free biosensing and imaging of cancer biomarkers. We have decorated single or dual targeting ligands on PLNPs for tumor-targeted imaging, and integrated other modal imaging agents into PLNPs for multimodal imaging. We have also employed specific functionalization for various biomedical applications including chemotherapy, photodynamic therapy, photothermal therapy, stem cells tracking and PL imaging-guided gene therapy. Besides, we have modified PLNPs with multiple functional units to achieve challenging metastatic tumor theranostics. The proposed design principle and comprehensive strategies show great potential in guiding the design of PLNPs nanoprobes and promoting further development of PLNPs in the fields of biological science and medicine. We conclude this Account by outlining the future directions to further promote the practical application of PLNPs. The novel protocols for the synthesis of small-size, monodisperse, and water-soluble PLNPs with high NIR PL intensity and superlong afterglow are the vibrant directions for the biomedical applications of PLNPs. In-depth theories and evidence on luminescence mechanism of PLNPs are highly desired for further improvement of their luminescence performance. Furthermore, other irradiations without tissue penetrating depth limit, such as X-ray, are encouraged for use in energy storage and re-excitation of PLNPs, enabling imaging in deep tissue in vivo and integrating other X-ray sensitized theranostic techniques such as computed tomography imaging and radiotherapy. Last but not least, PLNPs-based nanoprobes and the brand new hybrids of PLNPs with other nanomaterials show a bright prospect for accurate diagnosis and efficient treatment of diseases besides tumors.

One-Minute Preparation of Iron Foam-Drug Implant for Ultralow-Power Magnetic Hyperthermia-Based Combination Therapy of Tumors in Vivo.

The magnetic hyperthermia-based combination therapy (MHCT) is a powerful tumor treatment approach due to its unlimited tissue penetration depth and synergistic therapeutic effect. However, strong magnetic hyperthermia and facile drug loading are incompatible with current MHCT platforms. Herein, an iron foam (IF)-drug implant is established in an ultra-facile and universal way for ultralow-power MHCT of tumors in vivo for the first time. The IF-drug implant is fabricated by simply immersing IF in a drug solution at an adjustable concentration for 1 min. Continuous metal structure of IF enables ultra-high efficient magnetic hyperthermia based on eddy current thermal effect, and its porous feature provides great space for loading various hydrophilic and hydrophobic drugs via "capillary action". In addition, the IF has the merits of low cost, customizable size and shape, and good biocompatibility and biodegradability, benefiting reproducible and large-scale preparation of IF-drug implants for biological application. As a proof of concept, IF-doxorubicin (IF-DOX) is used for combined tumor treatment in vivo and achieves excellent therapeutic efficacy at a magnetic field intensity an order of magnitude lower than the threshold for biosafety application. The proposed IF-drug implant provides a handy and universal method for the fabrication of MHCT platforms for ultralow-power combination therapy.

Achieving Complete Tumor Clearance: A Minimalist Manganese Hydrogel for Magnetic Resonance Imaging-Guided Synergetic Microwave Ablation and Chemodynamic Therapy.

The combination of microwave ablation (MWA) and chemodynamic therapy (CDT) presents a promising strategy for complete eradication of residual tumor after MWA. However, it remains challenging and urgent to develop a facile, biocompatible, and imaging-guided platform for the achievement of this goal. Herein, a minimalist manganese hydrogel (ALG-Mn hydrogel) is proposed for synergistic MWA and CDT to completely eradicate tumor in vivo. The ALG-Mn hydrogel is prepared using a simple mixing method and exhibits excellent syringeability, remarkable microwave sensitivity, and potent Fenton-like activity. By assisting in MWA procedures, the ALG-Mn hydrogel enables both elimination of primary tumor mass through enhanced MWA efficacy and eradication of potential residual tumor tissues via robust CDT. This approach achieves complete tumor clearance without additional drug loading. Furthermore, the paramagnetic Mn2+ component allows real-time dynamic visualization of the ALG-Mn hydrogel at the tumor site via magnetic resonance imaging. To the best of knowledge, the proposed ALG-Mn hydrogel represents the minimalist biocompatible platform for imaging-guided synergistic MWA and CDT toward achieving complete tumor clearance.

Highly Sensitive Early Diagnosis of Kidney Damage Using Renal Clearable Zwitterion-Coated Ferrite Nanoprobe via Magnetic Resonance Imaging In Vivo.

Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T1 relaxivity (12.52 mm-1s-1), a small hydrodynamic size (6.43 nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.

A hemicyanine-based near-infrared fluorescent probe with large Stokes shift for non-invasive bioimaging of brown adipose tissue.

Brown adipose tissue (BAT), characterized by the presence of numerous mitochondria, plays a key role in metabolism and energy expenditure. Accurately reporting the presence and activation of BAT is beneficial to study obesity, diabetes, and other metabolic disorders. Near-infrared (NIR) fluorescence imaging has the advantages of high sensitivity, non-radioactivity, and simple operation. However, most NIR probes for BAT imaging exhibit small Stokes shifts, which may lead to self-quenching, reducing the signal-to-noise ratio, and introducing cross-talk. Herein, we rationally designed and synthesized a series of hemicyanine-based NIR fluorescent probes HCYBAT-1-3. Among them, HCYBAT-1 demonstrated favorable properties such as near-infrared emission (776 nm), large Stokes shift (139 nm), good biocompatibility and specific mitochondrial targeting (Pearson's colocalization coefficient of 0.87). Meanwhile, HCYBAT-1 was successfully employed to differentiate BAT from white adipose tissue (WAT). Quantitative analysis of NIR fluorescent images showed that HCYBAT-1 could be used for real-time monitoring of BAT activation in mice stimulated by norepinephrine (NE) and cold exposure. Overall, probe HCYBAT-1 showcased its efficacy in non-invasive evaluation of BAT metabolism in vivo with high selectivity and sensitivity.

Bismuth drug-inspired ultra-small dextran coated bismuth oxide nanoparticles for targeted computed tomography imaging of inflammatory bowel disease.

Bismuth (Bi)-based computed tomography (CT) imaging contrast agents (CAs) hold significant promise for diagnosing gastrointestinal diseases due to their cost-effectiveness, heightened sensitivity, and commendable biocompatibility. Nevertheless, substantial challenges persist in achieving an easy synthesis process, remarkable water solubility, and effective targeting ability for the potential clinical transformation of Bi-based CAs. Herein, we show Bi drug-inspired ultra-small dextran coated bismuth oxide nanoparticles (Bi2O3-Dex NPs) for targeted CT imaging of inflammatory bowel disease (IBD). Bi2O3-Dex NPs are synthesized through a simple alkaline precipitation reaction using bismuth salts and dextran as the template. The Bi2O3-Dex NPs exhibit ultra-small size (3.4 nm), exceptional water solubility (over 200 mg mL-1), high Bi content (19.75 %), excellent biocompatibility and demonstrate higher X-ray attenuation capacity compared to clinical iohexol. Bi2O3-Dex NPs not only enable clear visualization of the GI tract outline and intestinal loop structures in CT imaging but also specifically target and accumulate at the inflammatory site in colitis mice after oral administration, facilitating a precise diagnosis and enabling targeted CT imaging of IBD. Our study introduces a novel and clinically promising strategy for synthesizing high-performance Bi2O3-Dex NPs for diagnosing gastrointestinal diseases.

Noninvasive Assessment of Kidney Injury by Combining Structure and Function Using Artificial Intelligence-Based Manganese-Enhanced Magnetic Resonance Imaging.

Contrast-enhanced magnetic resonance imaging (MRI) is seriously limited in kidney injury detection due to the nephrotoxicity of clinically used gadolinium-based contrast agents. Herein, we propose a noninvasive method for the assessment of kidney injury by combining structure and function information based on manganese (Mn)-enhanced MRI for the first time. As a proof of concept, the Mn-melanin nanoprobe with good biocompatibility and excellent T1 relaxivity is applied in MRI of a unilateral ureteral obstruction mice model. The abundant renal structure and function information is obtained through qualitative and quantitative analysis of MR images, and a brand new comprehensive assessment framework is proposed to precisely identify the degree of kidney injury successfully. Our study demonstrates that Mn-enhanced MRI is a promising approach for the highly sensitive and biosafe assessment of kidney injury in vivo.

Bioinspired BSA@polydopamine@Fe Nanoprobe with Self-Purification Capacity for Targeted Magnetic Resonance Imaging of Acute Kidney Injury.

Contrast-enhanced magnetic resonance imaging (CE-MRI) of acute kidney injury (AKI) is severely hindered by the poor targeting capacity and potential toxicity of current contrast agents. Herein, we propose one-step fabrication of a bovine serum albumin@polydopamine@Fe (BSA@PDA@Fe, BPFe) nanoprobe with self-purification capacity for targeted CE-MRI of AKI. BSA endows the BPFe nanoprobe with renal tubule-targeting ability, and PDA is capable of completely inhibiting the intrinsic metal-induced reactive oxygen species (ROS), which are always involved in Fe/Mn-based agents. The as-prepared nanoprobe owns a tiny size of 2.7 nm, excellent solubility, good T1 MRI ability, superior biocompatibility, and powerful antioxidant capacity. In vivo CE-MRI shows that the BPFe nanoprobe can accumulate in the renal cortex due to the reabsorption effect toward the serum albumin. In the AKI model, impaired renal reabsorption function can be effortlessly detected via the diminishment of renal cortical signal enhancement. More importantly, the administration of the BPFe nanoprobe would not aggravate renal damage of AKI due to the outstanding self-purification capacity. Besides, the BPFe nanoprobe is employed for CE-MR angiography to visualize fine vessel structures. This work provides an MRI contrast agent with good biosafety and targeting ability for CE-MRI of kidney diseases.

Purification-free synthesis of bright lactoglobulin@dye nanoprobe for second near-infrared fluorescence imaging of kidney dysfunction in vivo.

Kidney disease is currently prevalent worldwide but only shows insidious symptoms in the early stages. The second near-infrared window (NIR-II) fluorescence imaging has become a widely used preclinical technology for evaluating renal dysfunction due to its high resolution and sensitivity. However, bright renal clearable NIR-II fluorescence nanoprobes with a simple synthesis process are still lacking. Herein, we develop a lactoglobulin (LG)@dye nanoprobe for NIR-II fluorescence imaging of kidney dysfunction in vivo based on a purification-free method. The nanoprobe was synthesized by simply mixing LG and IR820 in aqueous solutions at 70 °C for 2 h based on the covalent interaction between the meso-Cl in IR820 and LG. The synthesized LG@IR820 nanoprobe has bright and stable NIR-II fluorescence, ultra-small size (<5 nm), low toxicity, and renal-clearable ability. The high reaction efficiency and pure aqueous reaction media make the synthesis method purification-free. In a unilateral ureteral obstruction mouse model, incipient renal dysfunction assessment was achieved by LG@IR820 nanoprobe, which couldn't be diagnosed with conventional kidney function indicators. This study provides a bright and purification-free NIR-II LG@IR820 nanoprobe to visualize kidney dysfunction at the early stage.

Nonmetallic graphite for tumor magnetic hyperthermia therapy.

Magnetic hyperthermia therapy (MHT) has garnered immense interest due to its exceptional spatiotemporal specificity, minimal invasiveness and remarkable tissue penetration depth. Nevertheless, the limited magnetothermal heating capability and the potential toxicity of metal ions in magnetic materials based on metallic elements significantly impede the advancement of MHT. Herein, we introduce the concept of nonmetallic materials, with graphite (Gra) as a proof of concept, as a highly efficient and biocompatible option for MHT of tumors in vivo for the first time. The Gra exhibits outstanding magnetothermal heating efficacy owing to the robust eddy thermal effect driven by its excellent electrical conductivity. Furthermore, being composed of carbon, Gra offers superior biocompatibility as carbon is an essential element for all living organisms. Additionally, the Gra boasts customizable shapes and sizes, low cost, and large-scale production capability, facilitating reproducible and straightforward manufacturing of various Gra implants. In a mouse tumor model, Gra-based MHT successfully eliminates the tumors at an extremely low magnetic field intensity, which is less than one-third of the established biosafety threshold. This study paves the way for the development of high-performance magnetocaloric materials by utilizing nonmetallic materials in place of metallic ones burdened with inherent limitations.

Ultrasmall catechol-PEG-anchored ferrite nanoparticles for highly sensitive magnetic resonance angiography.

Highly sensitive iron oxide nanoparticles with stable, safe and efficient surface functionalization, as potential substitutes for gadolinium-based contrast agents (GBCAs) with increasing biosafety concerns, exhibit great potential for high-performance magnetic resonance angiography (MRA). Herein, we developed ultrasmall catechol-PEG-anchored ferrite nanoparticles (PEG-UMFNPs) for highly sensitive MRA. The obtained nanoprobe has a high T1 relaxivity value (7.2 mM-1 s-1) due to its ultrasmall size and Mn doping. It has a suitable hydrodynamic size of 20 nm, which prevents rapid vascular extravasation and renal clearance and prolongs its blood circulation time. In vivo MRA at 3.0 T using the nanoprobe shows that the arteries and veins of rats, even blood vessels as small as 0.32 mm, are distinctly visible, and the contrast enhancement can last for at least 1 h. In addition, due to the outstanding contrast enhancement and long circulation time, the stenosis and recanalization process of the rat's carotid artery can be continuously monitored with a single injection of the nanoprobe. Our study indicates that PEG-UMFNPs are outstanding MR imaging nanoprobes that can be used to diagnose vascular diseases without the biosafety issues of GBCAs.

Gram-Scale Synthesis of Renal-Clearable Tantalum Nanodots with High Water Solubility for Computed Tomography Imaging In Vivo.

Tantalum (Ta) emerges as a promising element for advanced computed tomography (CT) imaging probes owing to its high X-ray attenuation coefficient and excellent biocompatibility. Nevertheless, the synthesis of renally clear Ta-based imaging probes through simple methods remains a significant challenge. Herein, we introduce a simple and gram-scale approach for the synthesis of renal-clearable Ta nanodots with high water solubility for CT imaging in vivo. The Ta nanodots, coordination polymers, are fabricated via coordination reactions involving Ta(OH)5, citric acid (CA), and hydrogen peroxide. The Ta nanodots exhibit an ultrasmall hydrodynamic diameter (2.8 nm), high water solubility (1.88 g/mL, 688 mg Ta/mL), superior X-ray absorption capacity, gram-scale production capability (>10 g in lab synthesis), renal-clearable ability, and good biocompatibility. The Ta nanodots possess superior CT imaging efficacy across diverse tube voltages, enabling highly sensitive gastrointestinal CT imaging, renal CT imaging, and CT angiography (CTA). Moreover, Ta nanodots maintain robust CT imaging capabilities even at high X-ray energies, and Ta nanodots-based spectral CT achieves metallic artifacts-minimized CTA. The proposed Ta nanodots present substantial potential as a potent CT imaging probe for diagnosing various diseases.

Metallic artifacts-free spectral computed tomography angiography based on renal clearable bismuth chelate.

Computed tomography angiography (CTA) is one of the most important diagnosis techniques for various vascular diseases in clinic. However, metallic artifacts caused by metal implants and calcified plaques in more and more patients severely hinder its wide applications. Herein, we propose an improved metallic artifacts-free spectral CTA technique based on renal clearable bismuth chelate (Bi-DTPA dimeglumine) for the first time. Bi-DTPA dimeglumine owns the merits of ultra-simple synthetic process, approximately 100% of yield, large-scale production capability, good biocompatibility, and favorable renal clearable ability. More importantly, Bi-DTPA dimeglumine shows superior contrast-enhanced effect in CTA compared with clinical iohexol at a wide range of X-ray energies especially in higher X-ray energy. In rabbits' model with metallic transplants, Bi-DTPA dimeglumine assisted-spectral CTA can not only effectively mitigate metallic artifacts by reducing beam hardening effect under high X-ray energy, but also enables accurate delineation of vascular structure. Our proposed strategy opens a revolutionary way to solve the bottleneck problem of metallic artifacts in CTA examinations.

Bismuth Chelate-Mediated Digital Subtraction Angiography.

Digital subtraction angiography (DSA) is considered the "gold standard" for the diagnosis of vascular diseases. However, the contrast agents used in DSA are limited to iodine (I)-based small molecules, which are unsuitable for patients with contraindications. Here, iodine-free DSA utilizing a bismuth (Bi) chelate, Bi-DTPA Dimeglumine, is proposed for vascular visualization for the first time. Bi-DTPA Dimeglumine possesses a simple synthesis process without the need for purification, large-scale production ability (over 200 g in the lab), superior X-ray imaging capability, renal clearance capacity, and good biocompatibility. Bi-DTPA-enhanced DSA can clearly display the arteries of the rabbit's head and lower limbs, with a minimum vascular resolution of 0.5 mm. The displayed integrity of terminal vessels by Bi-DTPA-enhanced DSA is superior to that of iopromide-enhanced DSA. In a rabbit model of thrombotic disease, Bi-DTPA Dimeglumine-enhanced DSA enables the detection of embolism and subsequent reevaluation of vascular conditions after recanalization therapy. This proposed iodine-free DSA provides a promising and universal approach for diagnosing vascular diseases.

Magnetic Resonance Angiography with Hour-Scale Duration after Single Low-Dose Administration of Biocompatible Gadolinium Oxide Nanoprobe.

Long-term contrast-enhanced angiography offers significant advantages in theranostics for diverse vascular diseases, particularly in terms of real-time dynamic monitoring during acute vascular events; However, achieving vascular imaging with a duration of hours through a single administration of low-dose contrast agent remains challenging. Herein, a hyaluronic acid-templated gadolinium oxide (HA@Gd2O3) nanoprobe-enhanced magnetic resonance angiography (MRA) is proposed to address this bottleneck issue for the first time. The HA@Gd2O3 nanoprobe synthesized from a facile one-pot biomineralization method owns ultrasmall size, good biocompatibility, optimal circulation half-life (≈149 min), and a relatively high T1 relaxivity (r1) under both clinical 3 T (8.215 mM-1s-1) and preclinical 9.4 T (4.023 mM-1s-1) equipment. The HA@Gd2O3 nanoprobe-enhanced MRA highlights major vessels readily with significantly improved contrast, extended imaging duration for at least 2 h, and ultrahigh resolution of 0.15 mm under 9.4 T, while only requiring half clinical dosage of Gd. This technique can enable rapid diagnosis and real-time dynamic monitoring of vascular changes in a model of acute superior mesenteric vein thrombosis with only a single injection of nanoprobe. The HA@Gd2O3 nanoprobe-enhanced MRA provides a sophisticated approach for long-term (hour scale) vascular imaging with ultrahigh resolution and high contrast through single administration of low-dose contrast agent.

A Non-Metallic Nanozyme Ameliorates Pulmonary Hypertension Through Inhibiting ROS/TGF-ß1 Signaling.

Pulmonary hypertension (PH) is a life-threatening cardiovascular disease with a lack of effective treatment options. Nanozymes, though promising for PH therapy, pose safety risks due to their metallic nature. Here, a non-metallic nanozyme is reported for the treatment of monocrotaline (MCT)-induced PH with a therapeutic mechanism involving the ROS/TGF-ß1 signaling. The synthesized melanin-polyvinylpyrrolidone-polyethylene glycol (MPP) nanoparticles showcase ultra-small size, excellent water solubility, high biocompatibility, and remarkable antioxidant capacity. The MPP nanoparticles are capable of effectively eliminating ROS in isolated pulmonary artery smooth muscle cells (PASMCs) from PH rats, and significantly reduce PASMC proliferation and migration. In vivo results from a PH model demonstrate that MPP nanoparticles significantly increase pulmonary artery acceleration time, decrease wall thickening and PCNA expression in lung tissues, as evidenced by echocardiograpy, histology and immunoblot analysis. Additionally, MPP nanoparticles treatment improve running capacity, decrease Fulton index, and attenuate right ventricular fibrosis in MCT-PH rats by using treadmill test, picrosirius red, and trichrome Masson staining. Further transcriptomic and biochemical analyses reveal that inhibiting ROS-driven activation of TGF-ß1 in the PA is the mechanism by which MPP nanoparticles exert their therapeutic effect. This study provides a novel approach for treating PH with non-metallic nanozymes based on a well-understood mechanism.

Real-time detection of gastrointestinal leaks via bismuth chelate-enhanced X-ray gastroenterography.

Anastomotic leaks are among the most dreaded complications following gastrointestinal (GI) surgery, and contrast-enhanced X-ray gastroenterography is considered the preferred initial diagnostic method for GI leaks. However, from fundamental research to clinical practice, the only oral iodinated contrast agents currently available for GI leaks detection are facing several challenges, including low sensitivity, iodine allergy, and contraindications in patients with thyroid diseases. Herein, we propose a cinematic contrast-enhanced X-ray gastroenterography for the real-time detection of GI leaks with an iodine-free bismuth chelate (Bi-DTPA) for the first time. The Bi-DTPA, synthesized through a straightforward one-pot method, offers distinct advantages such as no need for purification, a nearly 100 % yield, large-scale production capability, and good biocompatibility. The remarkable X-ray attenuation properties of Bi-DTPA enable real-time dynamic visualization of whole GI tract under both X-ray gastroenterography and computed tomography (CT) imaging. More importantly, the leaky site and severity can be both clearly displayed during Bi-DTPA-enhanced gastroenterography in a rat model with esophageal leakage. The proposed movie-like Bi-DTPA-enhanced X-ray imaging approach presents a promising alternative to traditional GI radiography based on iodinated molecules. It demonstrates significant potential in addressing concerns related to iodine-associated adverse effects and offers an alternative method for visually detecting gastrointestinal leaks.

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.