Activity

Although the in vivo metabolic pathways of scutellarin, a traditional Chinese medicine, have been investigated via different liquid chromatography techniques, studies on the distribution and location of scutellarin within organ tissue sections have not been reported. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can generate in situ spatial distribution profiles for scutellarin and its metabolites in a kidney section. However, the direct detection of a small molecule (m/z less then 600) using conventional matrices often results in ion suppression and matrix interferences. In this study, we demonstrated a novel methodology using MALDI-MSI for the in situ spatial localization of scutellarin and its metabolites in kidney tissues by applying a binary matrix of graphene oxide (GO) and caffeic acid (CA). The results indicated that the binary matrix (GO/CA) significantly improved the detection efficiency of scutellarin and its metabolites with relatively high sensitivity, selectivity and reproducibility on tissue sections. This methodology was successfully applied to map scutellarin and its metabolites with MALDI-MSI in mouse kidney tissues. Specifically, scutellarin and scutellarein were found to be located in the cortex and medulla regions of the kidney with relatively high abundance, whereas the remaining metabolites appeared in the cortex with low abundance. We believe that the novel imaging methodology may also be used for the studies of cancerous tissues and inform the development of the future therapies of kidney tumors.Chemophotothermal combination therapy has emerged as a novel and promising strategy to treat cancer. To improve anticancer effectiveness and reduce systemic toxicity, it is essential to trigger drug release at tumor sites or within tumor cells for maximal drug exposure. Herein, we constructed gas-generating mesoporous silica nanoparticles (MSNs) that can load ammonium bicarbonate (ABC) and doxorubicin (DOX) within the pores, encapsulate indocyanine green (ICG) onto the polydopamine (PDA) layer, and modify the RGD peptide on the outer surface [denoted as M(abc)-DOX@PDA-ICG-PEG-RGD] for triggered drug release and targeted chemophotothermal combination therapy. Upon hyperthermia or low pH value, the encapsulated ABC can efficiently generate CO2 gas, thus enhancing the damage to the PDA layer and accelerating DOX release. In vitro experiments showed that the M(abc)-DOX@PDA-ICG-PEG-RGD significantly enhanced cellular uptake and cytotoxicity, and laser irradiation further increased the endocytic and cytotoxic effects. An in vivo study indicated that the nanoparticles can effectively accumulate at the tumor site and significantly inhibited tumor growth with no side-effects to the normal organs. Thus, this gas-generating MSN-based nanocarrier that can trigger drug release in response to laser irradiation or low pH value holds great potential in enhancing cancer chemophotothermal combination therapy.Whereas the reduction of N-heterocyclic carbene (NHC)-stabilised cymantrenyldibromoboranes, (NHC)BBr2Cym, in benzene results in the formation of the corresponding diborenes (NHC)2B2Cym2, a change of solvent to THF yields a borylene analogue of the form (NHC)2BCym, stabilised through a boratafulvene/borafulvenium conformation.Extracellular vesicles (EVs) represent an important mode of intercellular communication in both disease and developmental biology, exposing their potential in diagnostics and therapeutics. Recently, aptamer-based sensors, i.e. aptasensors, have been gradually applied in EV analysis due to their high selectivity and sensitivity. A fluorescent aptasensor enables easy readout by flow cytometry (FCM) and has more accuracy and convenience than conventional immunoassays for EV analysis. Here, we develop a fluorescent aptasensor-based method for quantitative analysis of nano-sized membrane vesicles by using high-resolution FCM. EVs as small as 100 nm are detected and quantified using a dual-staining procedure with the fluorescent aptasensor targeting CD63 and a cytoplasmic dye. Nano-sized EVs derived from bone marrow mesenchymal stem cells, human neural stem cells and human cornea epithelial cells are analyzed, and the result shows that their amount varies from 6.79 × 106 mL-1 to 2.08 × 108 mL-1 in culture media. The technique is also used to evaluate the bioactivity of EVs and, in the future, it may develop into a versatile tool to analyze and quantify EVs from a variety of biological objects with conventional cytometric instruments.Colorectal cancer (CRC) is the third most common cancer worldwide, and the prognosis of CRC is better with an earlier diagnosis. The presence of the gastrin-releasing peptide receptor (GRPR) has been documented in very high numbers on colorectal cancer cells, which makes it an ideal biomarker for the diagnosis of CRC. selleck kinase inhibitor Bombesin (BBN) peptide analogs have been extensively investigated for the imaging of human cancers with GRPR overexpression. Recently, we have reported a novel GRPR-targeted peptide named the GB-6 peptide. The GB-6 peptide based on BBN7-14 was designed to improve in vivo metabolic stability and decrease intestinal uptake. Meanwhile, GB-6 greatly retained the original GRPR-binding affinity of BBN7-14. In this study, the GB-6 peptide was labeled with radionuclide 99mTc or fluorescent dye for colorectal cancer imaging. In vitro receptor binding was studied in Caco-2 cells, and the GRPR targeting capacity and kinetics in vivo were evaluated using Caco-2 tumor xenografted mice models. In addition, cells and mice were also subjected to the corresponding BBN7-14 conjugations for comparison. The GB-6 peptide exhibited specific GRPR binding in vitro with a high affinity similar to that of BBN7-14. Furthermore, we observed that GB-6 showed higher tumor uptake and displayed lower intestinal activity than corresponding unmodified probe BBN7-14 in Caco-2 tumor-bearing mice. Overall, our studies demonstrated that GB-6 has the potential for early detection of CRC patients, and it may also serve as a valuable tool for non-invasive monitoring of colorectal tumor growth.