Epidermal growth factor receptor-targeted gelatin-based engineered nanocarriers for DNA delivery and transfection in human pancreatic cancer cells.
Type B gelatin-based engineered nanocarrier systems (GENS) have been used over the last several years as a non-condensing systemic and oral DNA delivery system. In this study, we have modified the surface of GENS with epidermal growth factor receptor (EGFR)-targeting peptide for gene delivery and transfection in pancreatic cancer cell lines. GENS were prepared by the solvent displacement method and the EGFR-targeting peptide was grafted on the surface using a hetero-bifunctional poly(ethylene glycol) (PEG) spacer. Plasmid DNA, encoding for enhanced green fluorescent protein (GFP), was efficiently encapsulated and protected from degrading enzymes in the control and surface-modified GENS. Upon incubation with EGFR over-expressing Panc-1 human pancreatic adenocarcinoma cells, the peptide-modified nanoparticles were found to be internalized efficiently by receptor-mediated endocytosis. Both quantitative and qualitative transgene expression efficiencies were significantly enhanced when plasmid DNA was administered with EGFR-targeted GENS relative to the control-unmodified gelatin or PEG-modified gelatin nanoparticle systems. Based on these preliminary results, EGFR-targeted GENS show tremendous promise as a safe and effective gene delivery vector with the potential to treat pancreatic cancer.
Magadala
Padmaja
P
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, Massachusetts 02115, USA.
Amiji
Mansoor
M
D000230:Adenocarcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D004587:Electrophoresis, Agar Gel; D066246:ErbB Receptors / Q000235:genetics*; D005780:Gelatin; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005818:Genetic Engineering / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008855:Microscopy, Electron, Scanning; D053769:Nanocapsules; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010957:Plasmids; D014162:Transfection
D004337:Drug Carriers; D053769:Nanocapsules; D049452:Green Fluorescent Proteins; D005780:Gelatin; D004247:DNA; D066246:ErbB Receptors