melitten and Brain-Neoplasms

Nanosized lipodisks with flat circular phospholipid bilayers surrounded by PEGylated edges have demonstrated promise in drug delivery. In the present work, a lipodisk-based paclitaxel and melittin co-delivery system functionalized with glycopeptide 9G-A7R (9G-A7R-Disk/PTX/melittin) was successfully constructed, in which melittin which was fully protected from proteolysis and hemolysis was effectively reduced. The ratio of paclitaxel to melittin in lipodisks could be accurately controlled through a film hydration-adsorption method. Paclitaxel combined with melittin showed synergism against U87 cells in vitro, and 9G-A7R-Disk/PTX/melittin demonstrated an enhanced anti-glioma effect in vivo, significantly prolonging the survival time of glioma-bearing mice. The results suggested a promising formulation for the co-delivery of paclitaxel/melittin and glioma-targeted therapy.

Topics: Animals; Brain Neoplasms; Drug Delivery Systems; Female; Glioma; Glycopeptides; Humans; Melitten; Mice; Mice, Nude; Nanoparticles; Paclitaxel; Xenograft Model Antitumor Assays

beta-Amyloid protein (A beta) is a member of a small group of proteins that accumulate as amyloid deposits in various tissues. It has recently been demonstrated that the toxicity of A beta toward some neural cells is caused by oxidative damage. Since all of the amyloid diseases are characterized by protein deposited in the antiparallel beta-sheet conformation, it was asked whether there is a common toxic mechanism. It is shown here that the protein components of other human amyloidoses, including amylin, calcitonin, and atrial natriuretic peptide, are all toxic to clonal and primary cells. The toxicity is mediated via a free radical pathway indistinguishable from that of A beta. Experiments with synthetic peptides suggest that it is the amphiphilic nature of the peptides generated by their beta structure rather than their beta structure per se that causes toxicity. These results tend to rule out the alternative that amyloid toxicity is exclusively mediated via specific cell surface receptors.

Topics: Amino Acid Sequence; Amyloid; Amyloid beta-Peptides; Animals; Atrial Natriuretic Factor; Brain Neoplasms; Calcitonin; Cell Line; Cell Survival; Flow Cytometry; Humans; Hydrogen Peroxide; Intercellular Signaling Peptides and Proteins; Islet Amyloid Polypeptide; L-Lactate Dehydrogenase; Melitten; Molecular Sequence Data; NADH, NADPH Oxidoreductases; Oligopeptides; Onium Compounds; p-Methoxy-N-methylphenethylamine; Peptide Fragments; Peptides; Protein Structure, Secondary; Rats; Structure-Activity Relationship; Tumor Cells, Cultured; Wasp Venoms