Cargando…

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

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 ta...

Descripción completa

Detalles Bibliográficos
Autores principales: Xie, Yuran, Killinger, Bryan, Moszczynska, Anna, Merkel, Olivia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273023/
https://www.ncbi.nlm.nih.gov/pubmed/27735873
http://dx.doi.org/10.3390/molecules21101334
_version_ 1783377288749907968
author Xie, Yuran
Killinger, Bryan
Moszczynska, Anna
Merkel, Olivia M.
author_facet Xie, Yuran
Killinger, Bryan
Moszczynska, Anna
Merkel, Olivia M.
author_sort Xie, Yuran
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6273023
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62730232018-12-28 Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine Xie, Yuran Killinger, Bryan Moszczynska, Anna Merkel, Olivia M. Molecules Article 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. MDPI 2016-10-10 /pmc/articles/PMC6273023/ /pubmed/27735873 http://dx.doi.org/10.3390/molecules21101334 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xie, Yuran
Killinger, Bryan
Moszczynska, Anna
Merkel, Olivia M.
Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
title Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
title_full Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
title_fullStr Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
title_full_unstemmed Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
title_short Targeted Delivery of siRNA to Transferrin Receptor Overexpressing Tumor Cells via Peptide Modified Polyethylenimine
title_sort targeted delivery of sirna to transferrin receptor overexpressing tumor cells via peptide modified polyethylenimine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273023/
https://www.ncbi.nlm.nih.gov/pubmed/27735873
http://dx.doi.org/10.3390/molecules21101334
work_keys_str_mv AT xieyuran targeteddeliveryofsirnatotransferrinreceptoroverexpressingtumorcellsviapeptidemodifiedpolyethylenimine
AT killingerbryan targeteddeliveryofsirnatotransferrinreceptoroverexpressingtumorcellsviapeptidemodifiedpolyethylenimine
AT moszczynskaanna targeteddeliveryofsirnatotransferrinreceptoroverexpressingtumorcellsviapeptidemodifiedpolyethylenimine
AT merkeloliviam targeteddeliveryofsirnatotransferrinreceptoroverexpressingtumorcellsviapeptidemodifiedpolyethylenimine