RESUMO
Triple-negative breast cancer (TNBC) has been listed as one of the most fatal diseases, and no effective targeting treatment is clinically available. Although CD44-targeting hyaluronic acid (HA) has been utilized as targeting ligands in many studies, no facile ways have been developed through HA self-assembly at the nanoparticle surface. Herein, we reported N-isopropylacrylamide-grafted chitosan-based nanoparticles self-assembling with HA (HA-NPs) through electrostatic forces and loaded with curcumin (CUR). The HA-NPs displayed pH-responsive properties due to the chemical modification of chitosan, and the preparation process was optimized by central composite design-response surface methodology. HA anchorage confers the vehicle with tumor-targeting capability. HA-NPs displayed more robust effects of inhibiting TNBC primary tumor growth than free CUR and a plain counterpart but without increased systemic cytotoxicity. In addition, in vivo pharmacokinetic studies showed that HA-NPs significantly increased the in vivo residence time of free CUR and improved the bioavailability of CUR. These findings suggested that chitosan-based HA-NPs may provide a feasible and unique strategy to achieve CD44 targeting and enhance its efficacy in vivo for the treatment of advanced TNBC.
RESUMO
Based on the network pharmacology and molecular docking method to explore the molecular mechanism of Shengjiang Powder in treating chronic tonsillitis in children. This research first based on the Traditional Chinese Medicine System Pharmacology(TCMSP) and the Bioinformatics Analysis Tools for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM), the effective active ingredients of the drugs contained in Shengjiang Powder were screened out by the pharmacokinetic(ADME) parameters, the targets were predicted, and then chronic tonsillitis disease in children targets were obtained by GeneCards database. Afterwards, the target protein names were standardized by the Uniprot database. The drug targets were matched with the disease targets to obtain the potential therapeutic targets of Shengjiang Powder. Cytoscape 3.8.0 software was used to screen out and construct the network diagram of "drug-components-core targets-disease". DAVID database and R language were used to conduct the enrichment analysis of core action targets. Finally, AutoDock software was used to conduct molecular docking between drug components with a high network medium value and core action targets. According to the findings, after standardized treatment, a total of 79 active ingredients of Shengjiang Powder were obtained; it was predicted to get 1 261 potential targets, 268 potential targets for treatment of chronic tonsillitis in children, and 29 core targets; and 81 entries of GO enrichment were determined(P<0.05), including 63 biological processes, 7 cell components, 11 molecular function items, 24 KEGG pathway enrichment items(P<0.05), mainly including cell cycle, inflammatory factors, viral infection, immune regulation and other signaling pathways. The results of molecular docking showed that main active components in Shengjiang Powder had a stable binding activity with the core targets. This study revealed the mechanism of Shengjiang Powder in the treatment of chronic tonsillitis in children, mainly by resisting virus, inhibiting inflammation, regulating immunity and other means to play a synergistic effect, so as to provide a theoretical basis for rational clinical application.