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Lipid nanoparticle-mediated co-delivery of siRNA and small molecule holds a great potential to treat metabolic dysfunction-associated steatotic liver disease (MASLD). However, targeted delivery of therapeutics to hepatocytes remains challenging. Taking the advantage of rising low density lipoprotein receptor/very-low density lipoprotein receptor (LDLR/VLDR) levels in MASLD, the biological fate of dinonylamine-ethylene glycol chlorophosphate-1-nonanol (DNNA-COP-NA) based lipid nanoparticles (LNPs) was oriented to liver tissues via apolipoprotein E (ApoE)-LDLR/VLDLR pathway. We then adopted a three-round screening strategy to optimize the formulation with both high potency and selectivity to deliver siRNA-HIF-1α (siHIF1α) and silibinin (SLB) payloads to hepatocytes. The optimized SLB/siHIF1α-LNPs mediates great siRNA delivery and transfection of hepatocytes. In high fat diet (HFD)- and carbon tetrachloride (CCl 4 )-induced mouse models of MASLD, SLB/siHIF1α-LNPs enabled the silencing of hypoxia inducible factor-1α (HIF-1α), a therapeutic target primarily expressed by hepatocytes, leading to significantly reduced inflammation and liver fibrosis synergized with SLB. Moreover, it is demonstrated the hepatocyte-targeting delivery of SLB/siHIF1α-LNPs has the potential to restore the immune homeostasis by modulating the population of Tregs and cytotoxic T cells in spleen. This proof-of-concept study enable siRNA and small molecule co-delivery to hepatocytes through intrinsic variation of targeting receptors for MASLD therapy., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Iron oxide nanoparticles (IONPs) have been developed as contrast agents for T 1 - or T 2 -weighted magnetic resonance imaging (MRI) on account of their excellent physicochemical and biological properties. However, general strategies to improve longitudinal relaxivity ( r 1 ) often decrease transverse relaxivity ( r 2 core-shell nanoparticles (NPs), which possess high T 1 and T 2 enhancement effect of IONPs remains a challenge. Here, we report interface regulation and size tailoring of a group of FePt@Fe 3 O 4 core-shell nanoparticles (NPs), which possess high r 1 and r 2 relaxivities. The increase of r 1 and r 2 is due to the enhancement of the saturation magnetization ( M s ), which is a result of the strengthened exchange coupling across the core-shell interface. In vivo subcutaneous tumor study and brain glioma imaging revealed that FePt@Fe 3 O 4 NPs can serve as a favorable T 1 - T 2 dual-modal contrast agent. We envision that the core-shell NPs, through interface engineering, have great potential in preclinical and clinical MRI applications.

Various functional nanomaterials have been fabricated as diagnostic and therapeutic nanomedicines; however, the nanoparticles closely interact with proteins when immersed in biological fluids, forming a "protein corona" that critically alters the biological identity of nanomedicine. Here, we developed a robust strategy to construct theranostic nanoprobes based on protein-corona-coated Fe 3 O 4 nanoparticles and biomineralization in the corona. Water-soluble carboxylic Fe 3 O 4 nanoparticles were prepared by treating oleate-capped Fe 3 O 4 nanoparticles with Lemieux-von Rudloff reagent. Bovine serum albumin (BSA) was used as a model protein to form a corona on the surface of Fe 3 O 4 nanoparticles, endowing the Fe 3 O 4 nanoparticles with biocompatibility and nonimmunogenicity. The protein corona also provides a template for biomimetic mineralization of Fe 3+ with tannic acid (TA) to construct Fe 3 O 4 @BSA-TAFe III nanoprobes. The TA-Fe(III) biominerals can not only act as photothermal therapy agents but also interact with unsaturated transferrin in plasma to form a "hybrid" corona, enabling the nanoprobes to target tumor cells through the mediation of transferrin receptors, which commonly overexpress on tumor cell membranes. Once taken in by tumor cells, the protonation of phenol hydroxyl groups in acidic lysosomes would lead to the release of Fe 3+ , inducing tumor cell death through a ferroptosis/apoptosis hybrid pathway. In addition, the released Fe 3+ can boost the T 1 -weighted MR imaging performance, and the Fe 3 nanoparticles serve as 4 nanoparticles serve as T 2 -weighted MR imaging contrast agents. It is thus believed that the current nanoprobes can realize the enhanced dual-modality MR imaging and combined therapy of tumors through controlling the protein corona and biomineralization.

A new type of gold nanoparticles-attached indium tin oxide electrode was made. By SEM and EDS, the as-prepared gold nanoparticles-modified ITO electrode was characterized. This modified electrode has been used for the determination of pirarubicin (THP) in urine by cyclic voltammetry. Compared to a bare ITO electrode, the modified electrode exhibited a marked enhancement in the current response. Liner calibration curves are obtained in the range 5×10-9mol/L∼1.5×10-6 mol/L with a detection limit of 1×10-9 mol/L. The percentage of the recoveries ranged from 99.3% to 106.3%. The practical analytic utility of the method is illustrated by quantitative determination of THP in urine. [ABSTRACT FROM AUTHOR]

It is the first time that Horseradish peroxidase (HRP) was successively immobilized on the magnetic cobalt nanoparticles modified ITO (indium tin oxide) electrode. Morphologies of electrode surface were featured by the field emission-scanning electron microscope (FSEM). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to characterize the modified process of electrode. Direct electrochemistry and electrocatalysis of HRP immobilized on nano-Co/ITO were investigated. The biosensor exhibited high sensitivity, good stability, and excellent electrocatalytic activity to the reduction of H2O2. Under the optimized experimental conditions, a calibration curve over 2.0×10-9∼2.0×10-8 mol l-1 and 2.0×10-7∼2.0×10-6 mol l-1, with a limit of detection of 1.9×10-9 mol l-1 was obtained. The apparent Michaelis-Menten constant (KMapp) for HRP/nano-Co/ITO electrode was calculated to be 0.79 mmol l-1, indicating a higher affinity of HRP attached on the modified electrode. [ABSTRACT FROM AUTHOR]

A novel functional electrode was obtained by implanting NH2+ into ITO film (NH2/ITO) for the first time. The NH2/ITO surface showed a better affinity to gold nanoparticles than bare ITO. Gold nanoparticles were deposited on the surface of NH2/ITO electrode (Au/NH2/ITO). The Au/NH2/ITO and NH2/ITO electrodes were used to observe the electrochemical behavior of Hemoglobin (Hb) immobilized on the electrodes surfaces. The peak current value of Hb immobilized on NH2/ITO increased compared with on bare ITO while peak current value of Hb immobilized on Au/NH2/ITO increased compared with on Au/ITO. Linkage between the -NH2 implanted into the ITO film and the -COOH of Hb was thought to be the reason for the increase of active Hb coverage on NH2/ITO compared with bare ITO. Increase of active Hb coverage on Au/NH2/ITO compare with Au/ITO was attributed to the different amount of gold nanoparticles deposited. Results showed the novel NH2/ITO and Au/NH2/ITO electrodes exhibited good stability, reproducibility besides selectivity and sensitivity. The electrode process of Hb immobilized on Au/NH2/ITO was quasi-reversible with adsorption. The electrode reaction rate constant ks and other related constants were determined. X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), and impedance spectra were used to characterize the different surfaces. [ABSTRACT FROM AUTHOR]

The immobilization of Hemoglobin (Hb) on Au-colloid associated with a 4-Aminothiophenol monolayer on a gold electrode was studied. The electrochemical behaviors of the modified electrode was characterized and investigated by electrochemical impedance spectroscopy (EIS) and cyclic voltammograms (CVs). Differnces among each modifying steps were observed. The results implied that Au colloid enlarged the surface of modified electrode so as to increase the immobilization amount of Hb. Some parameters of EIS have been discussed to fit results. This method shows good correlation for detection of Hb in a broad linear range and exhibits low detection limit. [ABSTRACT FROM AUTHOR]

Adsorption of cytochrome c (Cyt c) on a gold nanoparticle – modified gold electrode was studied by using cyclic voltammetry, electrochemical impedance spectroscopy and chronopotentiometry in a phosphate buffer solution. It is shown that the charge transfer resistance is directly proportional to the amount of adsorbed Cyt c. The effects of temperature and time on the course of adsorption were also studied. The trends obtained in ΔGADS showed that Cyt c was found to have a smaller affinity for the modified electrode as indicated by their smaller negative ΔGADS values. [ABSTRACT FROM AUTHOR]

Abstract: NH2 + ions implantation was performed at energy of 80keV with the ion dose of 5.0×1015 ionscm−2 for indium tin oxide (ITO) electrode, which formed a new electrode NH2/ITO. And then the electrode was immersed into the platinum nanoparticles (PtNPs) solution, in which PtNPs were successfully attached to the surface of NH2/ITO electrode through the strong electrostatic attraction formed between PtNPs and the NH2/ITO surface, resulting platinum nanoparticles-attached NH2 + ions implantation-modified ITO (PtNPs/NH2/ITO) electrode. Results of X-ray photoelectron spectra (XPS) and the water contact angle (WCA) measurements showed that the implanted NH2 + ions existed on the NH2/ITO surface. Scanning electron microscopy (SEM) analysis indicated that the attachment of PtNPs to ITO surface was improved after NH2 + ions implantation. Cyclic voltammetric measurements were carried out to investigate the electrochemical performance of the PtNPs/NH2/ITO electrode. It was found that the PtNPs/NH2/ITO electrode showed high electrochemical activities and displayed good electrocatalytic oxidation response to methanol. Therefore, the modified electrode could be applicable to be the sensor for detecting methanol. [Copyright &y& Elsevier]

Abstract: NH2 + ion implantation was performed at the energy of 80keV with fluence of 2×1016 ions·cm−2 for indium tin oxide (ITO) film coated glass, and the existence of amino group on the ITO surface was verified by Fourier transform infrared (FT-IR) spectra and X-ray photoelectron spectroscopy (XPS) analysis. The gold nanoparticles (AuNPs) have been fabricated on the surface of the obtained NH2 + ions implantation-modified ITO (NH2/ITO) film, resulting gold nanoparticles-attached NH2 + ions implantation-modified ITO (AuNPs/NH2/ITO) substrate. This ion implantation approach provides a useful strategy to attach AuNPs on the ITO surface with higher density without using certain organic binding molecules. Cyclic voltammtric results indicate that the AuNPs/NH2/ITO electrode shows excellent electrochemical properties, and thus this material is expected to have widely potential applications in electrochemical analysis and biosensors. [Copyright &y& Elsevier]