Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates

Abstract Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on...

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Autores principales:	Meenakshi Sharma, Naglaa Salem El-Sayed, Hung Do, Keykavous Parang, Rakesh Kumar Tiwari, Hamidreza Montazeri Aliabadi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1690c01a55bf420bbd6e05a491327a11
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spelling	oai:doaj.org-article:1690c01a55bf420bbd6e05a491327a112021-12-02T15:05:00ZTumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates10.1038/s41598-017-06381-y2045-2322https://doaj.org/article/1690c01a55bf420bbd6e05a491327a112017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06381-yhttps://doaj.org/toc/2045-2322Abstract Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach. At peptide:siRNA weight/weight ratio of 10:1 (N/P ≈ 13.6), almost all the peptides showed complete binding with siRNA, and at a w/w ratio of 20:1 (N/P ≈ 27.3), complete protection of siRNA from early enzymatic degradation was observed. Conjugated peptides and peptide/siRNA complexes did not show significant cytotoxicity in selected cell lines. The oleic acid-conjugated peptide showed the highest efficiency in siRNA uptake and silencing of kinesin spindle protein at peptide:siRNA w/w ratio of 80:1 (N/P ≈ 109). The siRNA internalization into non-tumorigenic kidney cells was negligible with all fatty acyl-peptide conjugates. These results indicate that conjugation of fatty acids to CGKRK could create an efficient delivery system for siRNA silencing specifically in tumor cells.Meenakshi SharmaNaglaa Salem El-SayedHung DoKeykavous ParangRakesh Kumar TiwariHamidreza Montazeri AliabadiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Meenakshi Sharma Naglaa Salem El-Sayed Hung Do Keykavous Parang Rakesh Kumar Tiwari Hamidreza Montazeri Aliabadi Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates
description	Abstract Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach. At peptide:siRNA weight/weight ratio of 10:1 (N/P ≈ 13.6), almost all the peptides showed complete binding with siRNA, and at a w/w ratio of 20:1 (N/P ≈ 27.3), complete protection of siRNA from early enzymatic degradation was observed. Conjugated peptides and peptide/siRNA complexes did not show significant cytotoxicity in selected cell lines. The oleic acid-conjugated peptide showed the highest efficiency in siRNA uptake and silencing of kinesin spindle protein at peptide:siRNA w/w ratio of 80:1 (N/P ≈ 109). The siRNA internalization into non-tumorigenic kidney cells was negligible with all fatty acyl-peptide conjugates. These results indicate that conjugation of fatty acids to CGKRK could create an efficient delivery system for siRNA silencing specifically in tumor cells.
format	article
author	Meenakshi Sharma Naglaa Salem El-Sayed Hung Do Keykavous Parang Rakesh Kumar Tiwari Hamidreza Montazeri Aliabadi
author_facet	Meenakshi Sharma Naglaa Salem El-Sayed Hung Do Keykavous Parang Rakesh Kumar Tiwari Hamidreza Montazeri Aliabadi
author_sort	Meenakshi Sharma
title	Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates
title_short	Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates
title_full	Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates
title_fullStr	Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates
title_full_unstemmed	Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates
title_sort	tumor-targeted delivery of sirna using fatty acyl-cgkrk peptide conjugates
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1690c01a55bf420bbd6e05a491327a11
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Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates

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