Yanwei Du

Functional graphene oxide as a plasmid-based Stat3 siRNA carrier inhibits mouse malignant melanoma growth in vivo

Graphene oxide (GO) has attracted intensive interest in the biomedical field in recent years. We investigate whether the use of functional graphene oxide as an efficient delivery system for delivering specific molecular antitumor therapeutics in vivo could achieve a more excellent antitumor effect. Constitutive activation of signal transducer and activator of transcription 3 (Stat3) promotes survival in a wide spectrum of human cancers. In this paper, we study the in vivo behavior of graphene oxide chemically functionalized with polyethylenimine and polyethylene glycol (GO-PEI-PEG) as a plasmid-based Stat3-specific small interfering RNA (siRNA) carrier in mouse malignant melanoma. The in vivo results indicate significant regression in tumor growth and tumor weight after plasmid-based Stat3 siRNA delivered by GO-PEI-PEG treatment. Moreover, there was no significant side effect from GO-PEI-PEG treatment according to histological examination and blood chemistry analysis in mice. Thus, our work is the first success of using GO-PEI-PEG as a promising carrier for plasmid Stat3 siRNA delivery and down-regulation of Stat3 by a polymer-mediated vehicle and suggests the great promise of graphene in biomedical applications such as cancer treatment.

Panaxadiol Saponin and Dexamethasone Improve Renal Function in Lipopolysaccharide-Induced Mouse Model of Acute Kidney Injury

Background Acute kidney injury (AKI) is a serious complication of systemic inflammatory response syndrome (SIRS), which has a high mortality rate. Previous studies showed that panaxadiol saponin (PDS) and Dexamethasone have similar anti-inflammatory properties and protect cardiopulmonary function in lipopolysaccharide (LPS)-induced septic shock rats. In the present study, we investigated whether PDS or Dexamethasone has a similar role in improving kidney function in LPS-induced AKI mice. Methods and Results Mice subjected to LPS (10 mg/kg) treatment exhibited AKI demonstrated by markedly increased blood urea nitrogen and creatinine levels compared with controls (P<0.01). However, PDS and Dexamethasone induce similar reverse effects on renal function, such as reduced serum creatinine and blood urea nitrogen levels compared with the LPS group (P<0.05). PDS decreased the production and release of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by inhibiting the NF-κB signaling pathway, down-regulating inducible nitric oxide synthase protein expression levels and inhibiting oxidative stress. In most anti-AKI mechanisms, PDS and dexamethasone were similar, but PDS are better at inhibition of TNF production, promote SOD activity and inhibition of IKB phosphorylation. In addition, nuclear glucocorticoid receptor expression was markedly enhanced in PDS and Dexamethasone treatment groups. Further research is required to determine whether PDS can combine with the glucocorticoid receptor to enter the nucleus. Conclusion This study demonstrated that PDS and dexamethasone have similar reverse amelioration for renal functions, and have potential application prospects in the treatment of sepsis-induced AKI.

Multi-functionalized graphene oxide complex as a plasmid delivery system for targeting hepatocellular carcinoma therapy

A novel efficient graphene-based gene delivery vector was synthesized by continuous covalent functionalization of graphene oxide (GO) with polyethylenimine (PEI), polyethylene glycol (PEG) and folic acid (FA), followed by loading si-Stat3 via electrostatic adsorption (GO–PEI–PEG–FA/si-Stat3). We investigated the effect of changing the content of PEI in the complex on the effective diameter and transfection efficiency. It was found that as the PEI content in the complex increased, the effective diameter was reduced until a point where it remained almost unchanged and the transfection efficiency of complex became higher. The results also showed that the transfection efficiency is relatively high with the content of PEI in the complex at 61 wt% without any obvious cytotoxicity. At the same time, the stability of the complex in physiological conditions was improved. The GO–PEI–PEG–FA/si-Stat3 complex exhibited an excellent ability to silence Stat3 expression for targeting tumor hepatocellular carcinoma in vitro.

Plasmid-Based Stat3 siRNA Delivered by Functional Graphene Oxide Suppresses Mouse Malignant Melanoma Cell Growth.

RNA interference (RNAi) has been used for cancer gene therapy in recent years. However, the application of RNAi is hindered in the absence of safe and efficient gene delivery. In this article, a novel vehicle of graphene oxide functionalized with polyethylenimine and polyethylene glycol (GO-PEI-PEG) was successfully synthetized and then used to deliver plasmid-based Stat3 siRNA. The carrier can readily bind plasmid with high transfection efficiency. Moreover, molecular biology studies reveal that Stat3-related gene and protein expressions were significantly inhibited, suggesting that the formation of GO-PEI-PEG complexes could be utilized as a promising gene delivery in cancer therapy.

Quantitative proteomic study of myocardial mitochondria in urea transporter B knockout mice

In previous research, we showed that 16‐week‐old urea transporter B (UT‐B) null mice have an atrial–ventricular conduction block, and hypothesized myocardial mitochondrial dysfunction. To investigate the mechanism of this block, we examined the proteomic differences in the myocardial mitochondria of UT‐B null and wild‐type mice with nanoscale LC–MS/MS. Of 26 proteins clearly downregulated in the UT‐B null mice, 15 are involved in complexes I, III, IV, and V of the respiratory chain, which would strongly reduce the activity of the electron transport chain. Excess electrons from complexes I and III pass directly to O2 to generate ROS and deplete ROS‐scavenging enzymes. Myocardial intracellular ROS were significantly higher in UT‐B null mice than in wild‐type mice (p < 0.01), constituting an important cause of oxidative stress injury in the myocardia of UT‐B null mice. The mitochondrial membrane potential (ΔΨm) was also lower in UT‐B null mice than in wild‐type mice (p < 0.05), causing oxidative phosphorylation dysfunction of complex V and insufficient ATP in the myocardial cells of UT‐B null mice. HADHA (a trifunctional protein) and HSP60 were also downregulated in the UT‐B null myocardial mitochondria. These results confirm that mitochondrial dysfunction underlies the pathogenesis of the atrial–ventricular conduction block in UT‐B null mice.