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

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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.

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Acknowledgments

Padmaja Magadala is a Fellow in the Nanomedicine Science and Technology Interdisciplinary Graduate Education and Research Training (IGERT) program. This pre-doctoral program is supported by the National Cancer Institute (NCI) and the National Science Foundation (NSF). Scanning electron microscopy was performed at Northeastern University’s Electron Microscopy Center. We deeply appreciate the assistance of Mr. Luis Brito with the flow cytometry analysis. Flow cytometry studies were performed in Professor Vladimir Torchilin’s Lab at Northeastern University.

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  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, Massachusetts, 02115, USA

    Padmaja Magadala & Mansoor Amiji

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  1. Padmaja Magadala
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  2. Mansoor Amiji
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Correspondence to Mansoor Amiji.

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Magadala, P., Amiji, M. Epidermal Growth Factor Receptor-Targeted Gelatin-Based Engineered Nanocarriers for DNA Delivery and Transfection in Human Pancreatic Cancer Cells. AAPS J 10, 565–576 (2008). https://doi.org/10.1208/s12248-008-9065-0

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