The AAPS Journal

, 10:565

Epidermal Growth Factor Receptor-Targeted Gelatin-Based Engineered Nanocarriers for DNA Delivery and Transfection in Human Pancreatic Cancer Cells

Research Article

DOI: 10.1208/s12248-008-9065-0

Cite this article as:
Magadala, P. & Amiji, M. AAPS J (2008) 10: 565. doi:10.1208/s12248-008-9065-0

Abstract

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.

Key words

EGFP-N1 plasmid DNAEGFR-targeted deliveryPanc-1 human pancreatic adenocarcinoma cellstransgene expressiontype B gelatin nanoparticles

Copyright information

© American Association of Pharmaceutical Scientists 2008

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences, School of PharmacyNortheastern UniversityBostonUSA