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.

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.

Transform commercial magnetic materials into injectable gel for magnetic hyperthermia therapy in vivo.

Magnetic hyperthermia therapy of tumors employing magnetic materials has been greatly developed due to their low invasiveness, high specificity, few side effects and no limitation of tissue penetration depth. However, traditional nanoscale magnetocaloric materials exhibited the disadvantages of low tumor enrichment efficiency, complex preparation process and difficulty in large-scale production. While eddy current loss-based magnetic hyperthermia tumor ablation with metal implants faces shortcomings such as high invasiveness and low selectivity of tumor shape and volume. Herein, we developed injectable magnetic gels by adding commercial magnetic metal or metal oxide powders (CMMPs) into alginate-Ca2+ (ALG-Ca2+) gel through an ultra-simple mixing strategy for magneto-thermal therapy of tumors in vivo. The ALG-Ca2+ gel can not only turn the water-insoluble CMMPs into injectable gel, but also retain the inherent magnetic loss-based heating capacity. Besides, CMMPs in the gels are easily retained at the tumor site after peritumoral injection because of their large size and strong hydrophobicity, which benefits the efficiency and accuracy of the treatment and reduces side effects to the surrounding tissues. The prepared ALG-Ca2+-CMMPs give full play to the inherent magneto-thermal capacity of CMMPs, which possesses super high loading ability (>100 mg magnetic materials/mL), superior large-scale production capability (>1 kg in laboratory synthesis), low cost, satisfactory syringeability and biological safety. Collectively, this study provides a convenient and universal strategy for the construction of magnetocaloric materials for biological applications.

Non-invasive Diagnosis and Postoperative Evaluation of Carotid Artery Stenosis by BSA-Gd2O3 Nanoparticles-Based Magnetic Resonance Angiography.

Contrast-enhanced magnetic resonance angiography is a powerful and effective method to accurately diagnose carotid artery stenosis. Small molecular gadolinium (Gd)-based agents have reliable signal enhancement, but their short circulating time may result in a loss of image resolution due to insufficient vascular filling or contrast agent emptying. Here, we report an MRA imaging approach to diagnose carotid artery stenosis using long-circulating bovine serum albumin (BSA)-Gd2O3 nanoparticles (NPs). The BSA-Gd2O3 NPs synthesized by a simple biomineralization approach exhibit admirable monodispersity, uniform size, favorable aqueous solubility, good biocompatibility, and high relaxivity (14.86 mM-1 s-1 in water, 6.41 mM-1 s-1 in plasma). In vivo MRA imaging shows that outstanding vascular enhancement of BSA-Gd2O3 NPs (0.05 mmol Gd/kg, half the dose in the clinic) can be maintained for at least 2 h, much longer than Gd-DTPA. Vessels as small as 0.3 mm can be clearly observed in MRA images with high resolution. In a rat carotid artery stenosis model, the BSA-Gd2O3 NPs-based MRA enables the precise diagnosis of the severity and location and the therapeutic effect following the surgery of carotid artery stenosis, which provides a method for the theranostics of vascular diseases.

White tea alleviates non-alcoholic fatty liver disease by regulating energy expenditure and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease, which lacks effective treatments. Abnormal lipid metabolism and inflammation are the most prominent pathological manifestations of NAFLD. Recently, it has been reported that white tea extract (WTE) can regulate lipid metabolism in human adipocytes and liver cancer cells in vitro. However, its beneficial effects on NAFLD and the underlying mechanisms remain largely unknown. Here, we showed that WTE alleviated obesity, lipid accumulation, hepatic steatosis, and liver injury in a mouse model of NAFLD. Mechanistically, we demonstrated that WTE exerted the anti-NAFLD effect by decreasing the expression of genes involved in lipid transport and synthesis processes while activating genes associated with energy expenditure. In addition, a comparison of the transcriptional responses of WTE with that of green tea extract (GTE) revealed that WTE can not only regulate lipid metabolism and stress response like GTE but also regulate antioxidant and inflammatory pathways more effectively. Taken together, our findings demonstrate that WTE inhibits the progression of NAFLD in a mouse model and indicate that WTE can be a potential dietary intervention for NAFLD.

Biocompatible BSA-MnO2 nanoparticles for in vivo timely permeability imaging of blood-brain barrier and prediction of hemorrhage transformation in acute ischemic stroke.

Hemorrhage transformation (HT) is a frequent but maybe fatal complication following acute ischemic stroke due to severe damage of the blood-brain barrier (BBB). Quantitative BBB permeability imaging is a promising method to predict HT in stroke patients for a favorable prognosis. However, clinical gadolinium chelate-based magnetic resonance (MR) imaging of the stroke suffers from a relatively low sensitivity and potential side effects of nephrogenic systemic fibrosis and intracranial gadolinium deposition. Herein, BSA-MnO2 nanoparticles (BM NPs) fabricated by a facile disinfection-mimic method were employed for the permeability imaging of BBB in the stroke for the first time. The BM NPs showed a high T1 relaxivity (r1 = 5.9 mM-1 s-1), remarkable MR imaging ability, and good biocompatibility, allowing the noninvasive timely visualization of BBB permeability in the model rats of middle cerebral artery occlusion (MCAO). Furthermore, increased peak intensity, extended imaging duration, and expanded imaging region indicated by BM NPs in MR imaging showed a good prediction for the onset of HT in MCAO rats. Therefore, BM NPs hold an attractive potential to be an alternative biocompatible MR contrast agent for the noninvasive BBB permeability imaging in vivo, benefiting the fundamental research of diverse neurological disorders and the clinical treatment for stroke patients.

Green and Kilogram-Scale Synthesis of Fe Hydrogel for Photothermal Therapy of Tumors in Vivo.

Photothermal agents with good biocompatibility, high tumor accumulation efficiency, large-scale production ability, and low cost are crucial for potential photothermal treatment in clinic. Herein, we proposed a green and highly efficient strategy to fabricate a kilogram-scale alginate-Ca2+-Fe powder hydrogel (ALG-Ca2+-Fe) by turning commercial Fe powder into hydrogel for enhanced photothermal therapy. The ALG-Ca2+-Fe was formed by simply dispersing commercial Fe powder into the preformed alginate-Ca2+ hydrogel in a green and energy-/time-saving way. The hydrogel exhibited the advantages of ultrahigh loading capacity of Fe powder (>100 mg mL-1), excellent large-scale production capacity (>1 kg in lab synthesis), low cost (<1.7 $/kg), and good injectability. More importantly, large size and hydrophobicity endowed Fe powder with excellent tumor retention effect and minimal diffusion to surrounding tissues, greatly benefiting improving treatment efficiency and reducing side effects. In vivo and in vitro studies both proved that the large-scale produced ALG-Ca2+-Fe can be used for highly efficient and biosafe tumor treatment in vivo by simple noninvasive injection. The developed ALG-Ca2+-Fe with multiple superiors opens up a novel green way to develop efficient and safe photothermal therapeutic agents with great clinic transformation potential.