ABSTRACT
The ultimate goal in cancer therapy is achieving selective targeting of cancer cells. We report a novel delivery platform, based on nanoghosts (NGs) produced from the membranes of mesenchymal stem cells (MSCs). Encompassing MSC surface molecules, the MSC-NGs retained MSC-specific in vitro and in vivo tumor targeting capabilities and were cleared from blood-filtering organs. MSC-NGs were found to be biocompatible. Systemic administration of drug loaded MSC-NGs demonstrated 80% inhibition of human prostate cancer.
Subject(s)
Cell Membrane/chemistry , Mesenchymal Stem Cells/chemistry , Nanocapsules/chemistry , Peptide Fragments/administration & dosage , Peptide Fragments/pharmacokinetics , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Receptors, TNF-Related Apoptosis-Inducing Ligand/administration & dosage , Receptors, TNF-Related Apoptosis-Inducing Ligand/pharmacokinetics , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Male , Mice , Mice, Inbred C57BL , Mice, Nude , Nanocapsules/administration & dosage , Nanocapsules/ultrastructure , Organ Specificity , Particle Size , Tissue Distribution , Treatment OutcomeABSTRACT
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) may play important roles during hepatitis B virus (HBV) infection. In this study, we used a recombinant human soluble death receptor 5 (sDR5) to explore its effect in a mouse model of HBV-induced acute hepatitis. By measuring blood transaminase activity and hepatocyte apoptosis, we found that sDR5 could alleviate liver damage by blocking TRAIL-induced apoptosis of HBV-transfected hepatocytes. sDR5 injection at 16 mg/kg 24h before HBV transfection was the most effective. Additionally, we showed that sDR5 was equally effective in protecting liver injury as the Stronger Neo-Minophagen C (SNMC), a commonly used drug for patients with liver diseases. Thus, sDR5 represents a potential novel therapeutic drug for patients with fulminant hepatitis.
