lactoferrin and arginyl-glycyl-aspartic-acid

Glioblastoma multiforme (GBM) is the most common malignant brain tumor originating in the central nervous system in adults. Based on nanotechnology such as liposomes, polymeric nanoparticles, and lipid nanoparticles, recent research efforts have been aimed to target drugs to the brain.. In this study, lactoferrin- and arginine-glycine-aspartic acid (RGD) dual- ligand-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers (L/RT/V-NLCs) were introduced for GBM combination therapy. The physicochemical properties of L/R-T/V-NLCs such as particle size, zeta potential, and encapsulated efficiency are measured. The drug release profile, cellular uptake, cytotoxicity, tissue distribution, and antitumor activity of L/R-T/V-NLCs are further investigated in vitro and in vivo.. L/R-T/V-NLCs were stable with nanosize and high drug encapsulation efficiency. L/R-T/V-NLCs exhibited sustained-release behavior, high cellular uptake, high cytotoxicity and synergy effects, increased drug accumulation in the tumor tissue, and obvious tumor inhibition efficiency with low systemic toxicity.. L/R-T/V-NLCs could be a promising drug delivery system for glioblastoma chemotherapy.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Line, Tumor; Dacarbazine; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Lactoferrin; Lipids; Mice, Inbred BALB C; Nanostructures; Neoplasms, Neuroepithelial; Oligopeptides; Temozolomide; Tissue Distribution; Vincristine; Xenograft Model Antitumor Assays

Lactoferrin (LF) is an iron-binding secretory protein, which is distributed in the secondary granules of polynuclear lymphocytes as well as in the milk produced by female mammals. Although it has multiple functions, for example antimicrobial, immunomodulatory, antiviral, and anti-tumor metastasis activities, the receptors responsible for these activities are not fully understood. In this study, the binding epitopes for human LF were first isolated from a hexameric random peptide library displayed on T7 phage. Interestingly, two of the four isolated peptides had a representative cell adhesion motif, Arg-Gly-Asp (RGD), implying that human LF interacts with proteins with the RGD motif. We found that human LF bound to the RGD-containing human extracellular matrix proteins, fibronectin and vitronectin. Furthermore, human LF inhibited cell adhesion to these matrix proteins in a concentration-dependent manner but not to the RGD-independent cell adhesion molecule like laminin or collagen. These results indicate that a function of human LF is to block the various interactions between the cell surface and adhesion molecules. This may explain the multifunctionality of LF.

Topics: Amino Acid Motifs; Animals; Binding Sites; Cell Adhesion Molecules; Cell Line; Enzyme-Linked Immunosorbent Assay; Epitopes; Extracellular Matrix Proteins; Humans; Lactoferrin; Mice; Oligopeptides; Protein Binding