Immunological gadolinium-doped mesoporous carbon nanoparticles for tumor-targeted MRI and photothermal-immune co-therapy.

Photothermal therapy (PTT) is an effective and well-documented approach to thermally ablate tumors. However, the side effect of distal metastasis and recurrence limit its further expansion. At the same time as PTT was developed, the employment of imaging to monitor the treatment of tumors also became meaningful. Herein, as a proof of concept, gadolinium-doped mesoporous carbon nanoparticles (Gd-MCNs) were prepared as nanocarriers, MRI contrast agents, and PTT agents by a one-step hard template method, which realized Gd doping and carbon filling simultaneously, while retaining enough pore space for drug loading. After loading the immune adjuvant, R837, and the coating of tumor extracellular vesicle, the obtained biomimetic nanoparticles (EV@Gd-MCNs-R837) not only allowed tumor MRI, but also inhibited the primary tumor and its metastasis with long-term immune memory in vivo. This study provides proof for the potential of Gd-MCNs-based biomimetic nanoparticles for targeted PTT/immune-enhanced synergistic theranostic of tumors.

Pro-efferocytic macrophage membrane biomimetic nanoparticles for the synergistic treatment of atherosclerosis via competition effect.

Macrophages participate in many links in the pathological process of atherosclerosis (AS) and the regulation of influence of macrophages at the molecular level might be a new avenue for AS treatment. For this aim, the macrophage membrane biomimetic nanoparticles, derived from macrophage membrane coated SHP1i-loaded liposome NPs (MM@Lips-SHP1i) was designed. Due to the reservation of intrinsic membrane proteins and function from macrophages, the biomimic nanoparticles could effectively evade clearance by the immune system, prolong blood circulation time and actively tend and aggregate to atherosclerotic plaques. More importantly, in the plaque area, MM@Lips-SHP1i nanoparticles could compete with macrophages in vivo to bind with oxidized low-density lipoprotein (oxLDL) and lipopolysaccharide (LPS), reduce uptake of new lipids by macrophages, reduce foam cell formation, and inhibit the expression of pro-inflammatory cytokines. In addition, small molecule inhibitor of SHP-1, the downstream effector molecule of CD47 loaded in macrophage membrane biomimetic nanoparticles could interrupt CD47-SIRPα signal transduction in monocytes and macrophages, thereby enhancing the efferocytosis of macrophages, inhibiting the progression of plaque, achieving synergistic treatment of atherosclerosis. This work focuses on the key process in the formation of AS, macrophage foaming and chronic inflammation, and is based on the fact that macrophage membrane biomimetic nanoparticles can preserve the key surface proteins of macrophages closely related to the formation of AS, providing a new avenue to inhibit the progression of AS by utilizing the biological characteristics of macrophage membrane in macrophage membrane biomimetic nanoparticles.

Targeted Therapy of Atherosclerosis Vulnerable Plaque by ROS-Scavenging Nanoparticles and MR/Fluorescence Dual-Modality Imaging Tracing.

Purpose: Early diagnosis and treatment of atherosclerosis (AS) vulnerable plaque has important clinical significance for the prognosis of patients. In this work, the integrated diagnosis and treatment nanoparticles based on Gd-doped Prussian blue (GPB) were constructed for the fluorescence/MR dual-mode imaging and anti-ROS treatment of vulnerable AS plaques in vitro and in vivo. Methods: To fabricate the theranostic NPs, GPB was modified with water-soluble polymer polyethyleneimine (PEI), fluorescence molecule rhodamine (Rd), and targeted molecule dextran sulfate (DS) step by step via electrostatic adsorption to construct GPRD NPs. The fluorescence/MR imaging ability and various nano-enzymes activity of GPRD NPs were detected, and the biocompatibility and safety of GPRD were also evaluated. Subsequently, RAW264.7 cells and ApoE -/- model mice were used to evaluate the effect of GPRD NPs on the targeted dual-mode imaging and anti-ROS treatment of vulnerable plaque in vitro and in vivo. Results: The experimental results showed that our fabricated GPRD NPs not only displayed excellent MR/fluorescence dual-modality imaging of vulnerable plaque in vivo but also effectively utilized the nano-enzyme activity of GPB to inhibit the AS progress by ROS scavenging and the following reduction of inflammation, apoptosis, and foam cells' formation, providing a new avenue for the diagnosis and treatment of AS vulnerable plaque. Conclusion: The fabricated multimodal imaging nanoparticles with ROS-scavenging ability provided a new avenue for the diagnosis and treatment of AS vulnerable plaques.

Spin state engineering of spinel oxides by integration of Cr doping and a p-n junction for water oxidation.

Spinel Co3O4 has emerged as a promising electrocatalyst towards alkaline water oxidation, but its activity is restricted by the undesirable electronic configuration of the octahedral Co3+ site. Herein, we simultaneously manipulate Cr doping and p-n junction engineering on Co3O4 nanorods, which contributes to the formation of Co2+ and Ni3+ octahedral sites with optimal eg fillings, thus achieving a superior OER performance.

Cadmium-mediated miR-30a-GRP78 leads to JNK-dependent autophagy in chicken kidney.

Cadmium-mediated microRNAs have become a heavily researched topic. Few studies mention the regulation of autophagy by cadmium through microRNAs, especially regarding poultry. The kidney is one of the organs most severely affected by cadmium, as it is involved in the accumulation of metal ions; causing such types of damage as apoptosis, necrosis and autophagy to the body. However, the relationship between miR-30a and GRP78 in the chicken kidney during ER stress and autophagy via JNK has not been thoroughly elucidated to date. In our research, we randomly assigned 128 Hy-Line Brown laying chickens to four groups with different diet treatments. The four groups consisted of the control group (0.2 mg Se kg-1), the Se group (2 mg kg-1 of Na2SeO3), the Se + Cd group (150 mg kg-1 of CdCl2 and 2 mg kg-1 of Na2SeO3) and the Cd group (150 mg kg-1 of CdCl2). On the 90th day, we detected the expression of miR-30a, GRP78, ER stress-related genes, IRE-1-JNK and autophagy-related genes. Compared with the control group, the mRNA levels of IRE-1-JNK, ER stress-related genes, autophagy-related genes and GRP78 were significantly increased (P < 0.05), while the expression of miR-30a was significantly decreased (p < 0.05) in the Cd group. However, those changes were clearly alleviated in the Se + Cd group (p < 0.05). In summary, we demonstrated that Cd triggered an miR-30a-GRP78 signaling axis disorder, increasing ER stress and activating the IRE-1-JNK pathway, thereby promoting autophagy in the chicken kidney. Moreover, Se could antagonize the negative impact of Cd.

Inflammatory Response Occurs in Veins of Broiler Chickens Treated with a Selenium Deficiency Diet.

Selenium (Se) has been indicated to prevent chronic diseases including cancer, cardiovascular disease, and type 2 diabetes. However, a few studies have indicated that Se deficiency can induce vascular diseases. Thus, in the present study, we investigated the effect of Se deficiency on vascular pathology. A total of 60 male broiler chickens were randomly divided into 2 groups (n = 30). The control group (C group) was fed a basic diet, and the Se-deficient group (L group) was fed a Se-deficient, corn-soy-based diet. Changes in messenger RNA (mRNA) and protein levels of inflammatory factors and inflammation-related cytokines were examined by both RT-PCR and Western blot analysis. Our results indicate that the mRNA and protein levels of inflammatory factors and inflammation-related cytokines in the L group were significantly changed in the vein. In addition, principal component analysis (PCA) was used to define the most important parameters that could be used as key factors. The in vitro experiments also demonstrated that Se can enhance the anti-inflammatory ability of vein endothelial cells. In conclusion, Se deficiency induces an inflammatory response by modulating inflammatory factors and inflammation-related cytokines.

The Antagonistic Effect of Selenium on Lead-Induced Immune Dysfunction via Recovery of Cytokine and Heat Shock Protein Expression in Chicken Neutrophils.

Lead (Pb) is a ubiquitous and toxic heavy metal and it can damage the immune system in humans and animals. Many researchers have reported that Selenium (Se) could possess various pharmacological effects in mammals. However, few studies have been carried out to investigate the protective role of Se in birds, especially in chickens. In this study, we investigated the protective effects of Se against Pb-induced inflammatory responses and the expression of heat shock proteins (HSPs) in peripheral blood neutrophils. One hundred eighty Hy-Line brown chickens were randomly divided into the control group (Con group), Se supplementation group (+Se group), Pb supplementation group (+Pb group), and the Se and Pb compound group (Se+Pb group). On the 90th day of the experiment, the peripheral blood was collected to extract neutrophils, and then, the levels of HSPs and cytokines were examined. The results showed that, after Pb treatment, the levels of IL-(1ß, 1R, 4, 8, 10, and 12ß), TGF-ß4, and HSP (27, 40, 60, 70, and 90) mRNA were significantly increased and levels of IL-2 and IFN-γ mRNA were decreased compared with those in the control group. Compared with the control group, the protein levels of HSP60 and HSP70 were also increased in the Pb treatment group. Co-administration of Se (1 mg/kg/day) and Pb resulted in a reversal of the Pb-induced cytokine changes in neutrophils accompanied by a significant decrease in HSPs. Our study demonstrated that Pb could decrease the immune function via changing the expression of cytokines and HSPs in chicken neutrophils, but Se could relieve the toxic effect induced by Pb.

Effects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils.

Lead (Pb) is one of the most highly toxic metal pollutant that can cause damage to the immune system. It is known that selenium (Se) can antagonize heavy metals. To explore the toxic effects of Pb poisoning on bird immune cells, as well as the alleviating effects of Se on Pb, Se supplement and/or Pb poisoning chicken models were established. One hundred and eighty Hyline 7-day-old male chickens received either Se (1mg Se per kg of diet), Pb (350mg Pb per liter water) or Se+Pb in their diet and water for 90 days. Then, whole blood was collected from the four groups of chickens, and serum and neutrophils were isolated. The levels of Se and Pb in chicken serum, mRNA levels of 24 selenoproteins (GPX1, GPX2, GPX3, GPX4, Dio1, Dio2, Dio3, Txnrd1, Txnrd2, Txnrd3, SELS, SPS2, SELK, SELW1, SEP15, SEPX1, SELT, SELI, SELO, SELM, SEPN1, SEPP1, SELU, SELH) and inflammatory factors (TNF-α, COX-2, iNOS, NF-κB), and iNOS protein level in chicken neutrophils were determined, and protein-protein interaction prediction and principal component analysis were performed. The data showed that Pb exposure increased Pb content in serum, activated the NF-κB pathway, and increased the expression of selenoproteins in chicken neutrophils. Se supplements could reduce Pb concentration in serum, had a mitigative effect on the activation of the NF-κB pathway and further enhanced the upward trend of selenoprotein expression induced by Pb exposure. These results suggest that Se supplement could eliminate Pb in serum and alleviate the activation of the NF-κB pathway under Pb exposure by increasing the expression of selenoproteins.