Document Type
Article
Publication Date
7-21-2017
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.
Recommended Citation
Sharma M, El-Sayed NS, Do H, Parang K, Tiwari RK, Aliabadi HM. Tumor-targeted delivery of siRNA using fatty acyl-CGKRK peptide conjugates. Sci Rep. 2017;7:6093. doi:10.1038/s41598-017-06381-y.
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
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Amino Acids, Peptides, and Proteins Commons, Cancer Biology Commons, Chemical Actions and Uses Commons, Medicinal and Pharmaceutical Chemistry Commons, Other Chemicals and Drugs Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pharmaceutical Preparations Commons, Pharmaceutics and Drug Design Commons
Comments
This article was originally published in Scientific Reports, volume 7, issue 1, in 2017. DOI: 10.1038/s41598-017-06381-y