Intervaginal space injection of photothermal chemotherapy nanoparticles for facilitating tumor targeting and improving outcomes in mice.

Although numerous photothermal nanoparticles have been designed to improve the enhanced and permeability and retention (EPR) effect, the delivery of nanoparticles to the tumor site remains a major obstacle in cancer treatment. The interstital structure and its internal fluid that play an important role in material transmission, intercellular signal transduction, tissue morphology, immunity, tumor development, and disease diagnosis and treatment may be considered as a new route for drug delivery. Here, we prepared a nanoplatform composed of polydopamine (PDA), indocyanine green (ICG) as a photothermal agent, and paclitaxel (PTX) as a chemotherapeutic drug. The designed PDA-ICG nanoparticles displayed excellent photothermal conversion ability, with the synergistic effect of PTX, the growth of MDA-MB-231 cells was significantly suppressed with the cell viability of 6.19% in vitro. Taking advantage of bioimaging ability of ICG, tumor-targeting of the nanoparticles injected into the interstitial space was study, Compared with intravenous injection, nanoparticles better targeted the tumor based on the interstitial fluid flow in MBA-MD-231 bearing mice. Furthermore, the antitumor efficacy was studied in vivo. With the improved accumulation of PDA-ICG-PTX nanoparticles injected into the interstitial space and the synergistic effect of photothermal therapy and chemotherapy, tumor growth was inhibited without obvious side effects. These results demonstrated that interstitial space injection may be a superior administration route for tumor-targeting nanoparticles. The PDA-ICG-PTX nanoparticles delivered via the interstitial space exhibit great potential in the photothermal chemotherapy of cancers.

High-throughput LC-MS method for the rapid characterisation and comparative analysis of multiple ingredients of four hawthorn leaf extracts.

INTRODUCTION: The comprehensive component characterisation of Chinese herbal medicine is the premise of effectively driving the discovery of pharmacodynamic substances or new drugs in recent years. OBJECTIVE: To use the high-throughput liquid chromatography-mass spectrometry (LC-MS) approach to systematically characterise phytochemical compounds from four hawthorn leaf extracts, along with evaluating their classification. METHODS: In the present study, the compounds from 50% ethanol extract, macro porous resin extract, ethyl acetate extract and standard decoction of hawthorn leaves were completely analysed by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS). RESULTS: Eight-nine compounds were putatively identified by comparison with secondary MS data and available references. Of these compounds identified, 56 compounds were found for the first time in hawthorn leaves, which was somewhat inconsistent with the findings of other studies. It could be inferred that falconoid, organic acids and nitrogenous compounds were the most abundant in 50% ethanol extract and standard decoction extract, which were considered as better choices for extracting hawthorn leaves. CONCLUSIONS: This work developed a simple, accurate and rapid method for the compound identification of hawthorn leaves, which laid the basis for further discovering pharmacodynamic material basis or new drugs from hawthorn leaves.

UPLC-Q-TOF-MS based metabolomics study of hawthorn leaves in different geographical regions.

The quality evaluation of hawthorn leaves in different geographical regions derived from the dried leaves of Crataegus pinnatifida Bge. Var. Major N.E.Br. or Crataegus pinnatifida Bge., a common blood-activating and stasis-eliminating traditional Chinese medicine, has hardly been reported. In this study, the chemical comparison of 40 batches of hawthorn leaf samples collected from Hebei, Liaoning, Shandong and Shanxi Provinces was performed using an ultra-high performance liquid chromatography with electrospray ionization-tandem mass spectrometry-based metabolic profile and pattern recognition analysis approach. A total of 233 compounds were determined. Among them, 40 compounds were selected as potential metabolites responsible for the differential clustering, and the differential metabolite-based evaluation model was applied to well distinguish the origin of seven batches of hawthorn leaves sold on the market. Further analysis of the KEGG pathway showed that five core metabolites containing flavonoids and lignins were mainly involved in flavonoid biosynthesis, flavone and flavonol biosynthesis, and stilbenoid, diarylheptanoid and gingerol biosynthesis. Taking the content of flavonoids, core markers, as the evaluation basis, it was found that the quality of hawthorn leaves in Hebei and Liaoning was better. The study provides a reference for the rational utilization of hawthorn leaves, and highlights that the metabolomics-driven analysis method is more suitable for the quality evaluation of traditional Chinese medicine.

Fingerprint and multi-ingredient quantitative analyses for quality evaluation of hawthorn leaves and Guang hawthorn leaves by UPLC-MS

ABSTRACT This paper aimed to evaluate the quality of hawthorn leaves and Guang hawthorn leaves by an UPLC-MS method from two aspects, fingerprint analysis and multi-ingredient quantification. Chromatographic separation was carried out on an UPLC system, the standardized characteristic fingerprints was established by Similarity Evaluation System for chromatographic fingerprinting of traditional Chinese medicine and cluster analysis. Eight components were simultaneously determined by mass spectrometry in multiple reaction-monitoring mode. The method was validated in terms of linearity (R2 > 0.9971), intraday and interday precision (RSD < 2.0%), repeatability (RSD < 2.3%), stability (RSD < 2.5%) and recovery (96.2-103.8%). The developed method was successfully applied to the quality evaluation between hawthorn leaves and Guang hawthorn leaves, and there were differences in the component and the content, hawthorn leaves and Guang hawthorn leaves cannot substitute each other in clinical medication.

Sonic hedgehog expression correlates with distant metastasis in pancreatic adenocarcinoma.

OBJECTIVES: To investigate the expression and clinical significance of Sonic hedgehog (Shh) in pancreatic adenocarcinoma. METHODS: The expression of Shh protein was examined in 34 surgical specimens of primary pancreatic adenocarcinoma, 21 nonmalignant specimens of the pancreas by immunohistochemistry streptavidin-perosidase (SP) method. In addition, semiquantitative reverse transcriptase polymerase chain reaction was carried out to analyze Shh mRNA expression in 22 pairs of freshly resected pancreatic adenocarcinoma tissues and their adjacent nontumorous tissues. RESULTS: The positive expression rate of Shh protein was 64.7% (22/34) in 34 surgical specimens of primary pancreatic adenocarcinoma and 0% (0/21) in 21 nonmalignant specimens of the pancreas. The expression rate of Shh was higher in pancreatic adenocarcinoma tissues than that of nonmalignant pancreatic tissues (χ2 = 22.647, P = 0.000). Sonic hedgehog protein expression correlated with TNM stages and distant metastasis. Moreover, the expression levels of Shh mRNA were higher in pancreatic adenocarcinoma tissues than that of the matched adjacent nontumorous tissues. CONCLUSIONS: Sonic hedgehog might play a pivotal role during tumorigenesis of pancreatic adenocarcinoma, and high Shh expression might be associated with the malignant potential of pancreatic cancer.