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Molecules 2016, 21(10), 1334;

Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine

Department of Pharmaceutical Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201, USA
Van Andel Institute, Grand Rapids, MI 49503, USA
Department of Pharmacy, Ludwig-Maximilians Universität München, Butenandtstr. 5-13 (Haus B), D 81377 Munich, Germany
Author to whom correspondence should be addressed.
Academic Editor: Wong Wai-Shiu
Received: 15 September 2016 / Revised: 30 September 2016 / Accepted: 4 October 2016 / Published: 10 October 2016
(This article belongs to the Special Issue Nucleic Acid-based Drug)
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The use of small interference RNA (siRNA) to target oncogenes is a promising treatment approach for cancer. However, siRNA cancer therapies are hindered by poor delivery of siRNA to cancer cells. Transferrin receptor (TfR) is overexpressed in many types of tumor cells and therefore is a potential target for the selective delivery of siRNA to cancer cells. Here, we used the TfR binding peptide HAIYPRH (HAI peptide) conjugated to cationic polymer branched polyethylenimine (bPEI), optimized the coupling strategy, and the TfR selective delivery of siRNA was evaluated in cells with high (H1299) and low TfR expression (A549 and H460). The HAI-bPEI conjugate exhibited chemico-physical properties in terms of size, zeta-potential, and siRNA condensation efficiency similar to unmodified bPEI. Confocal microscopy and flow cytometry results revealed that HAI-bPEI selectively delivered siRNA to H1299 cells compared with A549 or H460 cells. Moreover, HAI-bPEI achieved more efficient glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene knockdown in H1299 cells compared with bPEI alone. However, despite optimization of the targeting peptide and coupling strategy, HAI-bPEI can only silence reporter gene enhanced green fluorescent protein (eGFP) at the protein level when chloroquine is present, indicating that further optimization of the conjugate is required. In conclusion, the HAI peptide may be useful to target TfR overexpressing tumors in targeted gene and siRNA delivery approaches. View Full-Text
Keywords: siRNA delivery; transferrin receptor; targeting; peptide; polyethylenimine siRNA delivery; transferrin receptor; targeting; peptide; polyethylenimine

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Xie, Y.; Killinger, B.; Moszczynska, A.; Merkel, O.M. Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine. Molecules 2016, 21, 1334.

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