Multifunctional gene delivery vectors containing different liver-targeting fragments for specifically transfecting hepatocellular carcinoma (HCC) cells.

Gene therapy is a promising strategy for HCC treatment, but it commonly faces the problem of low specificity in gene transfection. In this study, we designed and synthesized a series of peptide-based gene delivery vectors (H-01 to H-18) containing varied HCC cell-targeting fragments for specifically binding different receptors highly expressed on HCC cell membranes. The physicochemical properties of peptide vectors or peptide/DNA complexes were characterized, and the gene delivery abilities of peptide vectors were evaluated in HepG2 cell lines. The results showed that peptide vectors H-02 and H-09, which contained targeted fragments for ACE2 and c-Met receptors, respectively, could specifically transfect HCC cells in a highly -efficient manner in vitro. Furthermore, the liver-targeting function in vivo of Cy5.5 labeled H-02 (H-17) and H-09 (H-18) was investigated by fluorescence imaging.

Discovery of AI-2 Quorum Sensing Inhibitors Targeting the LsrK/HPr Protein-Protein Interaction Site by Molecular Dynamics Simulation, Virtual Screening, and Bioassay Evaluation.

Quorum sensing (QS) is a cell-to-cell communication mechanism that regulates bacterial pathogenicity, biofilm formation, and antibiotic sensitivity. Among the identified quorum sensing, AI-2 QS exists in both Gram-negative and Gram-positive bacteria and is responsible for interspecies communication. Recent studies have highlighted the connection between the phosphotransferase system (PTS) and AI-2 QS, with this link being associated with protein-protein interaction (PPI) between HPr and LsrK. Here, we first discovered several AI-2 QSIs targeting the LsrK/HPr PPI site through molecular dynamics (MD) simulation, virtual screening, and bioassay evaluation. Of the 62 compounds purchased, eight compounds demonstrated significant inhibition in LsrK-based assays and AI-2 QS interference assays. Surface plasmon resonance (SPR) analysis confirmed that the hit compound 4171-0375 specifically bound to the LsrK-N protein (HPr binding domain, KD = 2.51 × 10-5 M), and therefore the LsrK/HPr PPI site. The structure-activity relationships (SARs) emphasized the importance of hydrophobic interactions with the hydrophobic pocket and hydrogen bonds or salt bridges with key residues of LsrK for LsrK/HPr PPI inhibitors. These new AI-2 QSIs, especially 4171-0375, exhibited novel structures, significant LsrK inhibition, and were suitable for structural modification to search for more effective AI-2 QSIs.

Transferrin receptor targeting segment T7 containing peptide gene delivery vectors for efficient transfection of brain tumor cells.

Successful gene therapy for brain tumors are often limited by two important factors, the existence of blood brain barrier (BBB) and inefficient transfection of brain tumor cells. In this study, we designed a series of peptide-based gene delivery vectors decorated with T7 segment for binding the transferrin (Tf) receptors which were highly expressed on brain tumor cells, and evaluated their ability of gene delivery. The physicochemical properties of peptide vectors or peptide/DNA complexes were studied as well. The in vitro transfection efficiency was investigated in normal and glioma cell lines. Among these complexes, PT-02/DNA complexes showed the highest transfection efficiency in glioma cells and low cytotoxicity in normal cell lines, and it could transport DNA across the BBB model in vitro. Furthermore, PT-02/DNA could deliver pIRES2-EGFP into the brain site of zebrafish in vivo. The designed peptide vectors offered a promising way for glioma gene therapy.

[The effect of gallic acid extracted from leaves of Phyllanthus emblica on apoptosis of human hepatocellular carcinoma BEL-7404 cells].

OBJECTIVE: To explore the effect of gallic acid extracted from Leaves of Phyllanthus emblica on the apoptosis of BEL-7404 cells. METHODS: MTT assay was applied to detect the influence on prolifetation in vitro. Inverted microscope was utilized to observe the morphological changes after BEL-7404 cells were treated with gallic acid. Annexin V/PI double label method was used to detect earlier period apoptosis cells and Tunel was applied to calculate the apoptosis rates. RESULTS: Gallic acid could restrain the BEL-7404 cells proliferation at diffierent levels in a time and concentration dependent manner. The typical morphological changes of apoptosis were observed after BEL-7404 cells were treated with gallic acid. Annexin V/PI double label method and Tunel method showed that the viable apoptotic cell and apoptosis rates added as action time prolonged. CONCLUSION: Gallic acid can restrain the BEL-7404 cells proliferation and induce apoptosis, and its effect on apoptosis is time dependent.