Tumor-penetrating iRGD facilitates penetration of poly(floxuridine-ketal)-based nanomedicine for enhanced pancreatic cancer therapy.

Efficient intratumoral penetration is essential for nanomedicine to eradicate pancreatic tumors. Although nanomedicine can enter the perivascular space of pancreatic tumors, their access to distal tumor cells, aloof from the vessels, remains a formidable challenge. Here, we synthesized an acid-activatable macromolecular prodrug of floxuridine (FUDR)-poly(FUDR-ketal), engineered a micellar nanomedicine of FUDR, and intravenously co-administered the nanomedicine with the tumor-penetrating peptide iRGD for enhanced treatment of pancreatic tumor. A FUDR-derived mono-isopropenyl ether was synthesized and underwent self-addition polymerization to afford the hydrophobic poly(FUDR-ketal), which was subsequently co-assembled with amphiphilic DSPE-mPEG into the micellar nanomedicine with size of 12 nm and drug content of 56.8 wt% using nanoprecipitation technique. The acetone-based ketal-linked poly(FUDR-ketal) was triggered by acid to release FUDR to inhibit cell proliferation. In an orthotopic pancreatic tumor model derived from KPC (KrasLSL-G12D/+; Trp53LSL-R172H/+; Pdx1-Cre) cells that overexpress neuropilin-1 (NRP-1) receptor, iRGD improved penetration of FUDR nanomedicine into tumor parenchyma and potentiated the therapeutic efficacy. Our nanoplatform, along with iRGD, thus appears to be promising for efficient penetration and activation of acid-responsive nanomedicines for enhanced pancreatic cancer therapy.

Investigate the effect of honey on the absorption of seven active ingredients from wu-tou decoction in rats.

Wu-tou decoction has been used as a traditional Chinese medicine prescription for thousands of years. It comprises five herbs, namely Radix Aconiti Preparata, Ephedrae Herba, Astragali Radix, Glycyrrhiza Radix, and Paeoniae Radix Alba. In addition, the original prescription contains honey, but in modern research, the existence of honey is commonly ignored. The aim was to investigate the effect of absorption in rats after oral wu-tou decoction with or without honey. In this research, a rapid and sensitive UPLC-MS/MS method was investigated for the quantitative analysis of ephedrine, pseudoephedrine, paeoniflorin, calycosin-7-glucoside, glycyrrhizic acid, liquiritin, and benzoylmesaconine in rat plasma after single and continuous oral decoctions. The results of the pharmacokinetic parameters showed that Cmax , CL/F, AUC0-t , and AUC0-∞ in the honey group were significantly increased than those in the non-honey group except for ephedrine and pseudoephedrine. The same trend was observed regardless of single or continuous oral administrations. Research studies showed that honey could promote the absorption of some effective components in wu-tou decoction in rats, enhance bioavailability, and provide a theoretical basis for the scientific and rational compatibility of the original prescription.

Hyperuricemia causes pancreatic ß-cell death and dysfunction through NF-κB signaling pathway.

Accumulating clinical evidence suggests that hyperuricemia is associated with an increased risk of type 2 diabetes. However, it is still unclear whether elevated levels of uric acid can cause direct injury of pancreatic ß-cells. In this study, we examined the effects of uric acid on ß-cell viability and function. Uric acid solution or normal saline was administered intraperitoneally to mice daily for 4 weeks. Uric acid-treated mice exhibited significantly impaired glucose tolerance and lower insulin levels in response to glucose challenge than did control mice. However, there were no significant differences in insulin sensitivity between the two groups. In comparison to the islets in control mice, the islets in the uric acid-treated mice were markedly smaller in size and contained less insulin. Treatment of ß-cells in vitro with uric acid activated the NF-κB signaling pathway through IκBα phosphorylation, resulting in upregulated inducible nitric oxide synthase (iNOS) expression and excessive nitric oxide (NO) production. Uric acid treatment also increased apoptosis and downregulated Bcl-2 expression in Min6 cells. In addition, a reduction in insulin secretion under glucose challenge was observed in the uric acid-treated mouse islets. These deleterious effects of uric acid on pancreatic ß-cells were attenuated by benzbromarone, an inhibitor of uric acid transporters, NOS inhibitor L-NMMA, and Bay 11-7082, an NF-κB inhibitor. Further investigation indicated that uric acid suppressed levels of MafA protein through enhancing its degradation. Collectively, our data suggested that an elevated level of uric acid causes ß-cell injury via the NF-κB-iNOS-NO signaling axis.

Detection of label-free H2O2 based on sensitive Au nanorods as sensor.

A rapid, reproducible, cost-effective approaches for the detection of hydrogen peroxide has been developed based on the change of localized surface plasmon resonance (LSPR) peak of Au nanorods (NRs). Au NRs were prepared by silver ion-assisted seed-mediated method, which are characterized by UV-vis spectroscopy and transmission electron microscopy. The longitudinal plasmon band of Au nanorods is highly sensitive to their aspect ratios so that LSPR peak of Au NRs was shift with change of their aspect ratios. Hydrogen peroxide (H(2)O(2)) with high oxidation potential can decompose Au NRs. As a result, Au NRs can be shortened through an oxidation reaction by H(2)O(2). After shortening Au NRs, the LSPR peaks show blue shift. The LSPR peak of Au NRs displays the dependence of spectral shift on concentration of H(2)O(2). It provides a more simple and sensitive method for detecting H(2)O(2).

Multifunctional ZnO/Ag nanorod array as highly sensitive substrate for surface enhanced Raman detection.

A multifunctional ZnO/Ag nanorod arrays has been prepared to construct SERS-active and photocatalytic substrate by a hydrothermal method. The morphology, microstructure and optical properties of ZnO/Ag nanorod arrays are characterized by X-ray diffraction spectra, field emission scanning electron microscopy, energy-dispersive, ultraviolet-visible (UV-vis) absorption and photoluminescence measurement to confirm the successful Ag deposition on the ZnO nanorod arrays. Such arrays exhibit strong and reproducible SERS signals of the Raman probe molecules. The mechanism of SERS enhancement was discussed due to the formation of interfacial electric field between ZnO nanorods and Ag. Furthermore, ZnO/Ag nanorod arrays also show catalytic properties by photocatalytic degradation of target molecules adsorbed to the substrate, which provides promising application for detecting and eliminating organic pollutant.