Targeted delivery of siRNA to activated T cells via transferrin-polyethylenimine (Tf-PEI) as a potential therapy of asthma.

Abstract

Asthma is a worldwide health problem. Activated T cells (ATCs) in the lung, particularly T helper 2 cells (Th2), are strongly associated with inducing airway inflammatory responses and chemoattraction of inflammatory cells in asthma. Small interfering RNA (siRNA) as a promising anti-sense molecule can specifically silence inflammation related genes in ATCs, however, lack of safe and efficient siRNA delivery systems limits the application of siRNA as a therapeutic molecule in asthma. Here, we designed a novel pulmonary delivery system of siRNA, transferrin-polyethylenimine (Tf-PEI), to selectively deliver siRNA to ATCs in the lung. Tf-PEI polyplexes demonstrated optimal physicochemical properties such as size, distribution, zeta-potential, and siRNA condensation efficiency. Moreover, in vitro studies showed significantly enhanced cellular uptake and gene knockdown mediated by Tf-PEI polyplexes in human primary ATCs. Biodistribution of polyplexes in a murine asthmatic model confirmed that Tf-PEI polyplexes can efficiently and selectively deliver siRNA to ATCs. In conclusion, the present work proves the feasibility to target ATCs in asthma via Tf receptor. This strategy could potentially be used to design an efficient siRNA delivery system for asthma therapy.

• Authors: Yuran Xie, Na Hyung Kim, Venkatareddy Nadithe, Dana Schalk, Archana Thakur, Ayşe Kılıç, Lawrence G Lum, David J P Bassett, Olivia M Merkel
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 229 Pg. 120-129 (05 10 2016) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 27001893 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• RNA, Small Interfering
• Receptors, Transferrin
• Transferrin
• Polyethyleneimine
• Glyceraldehyde-3-Phosphate Dehydrogenases

Topics

• Animals
• Asthma (metabolism, therapy)
• Glyceraldehyde-3-Phosphate Dehydrogenases (genetics)
• Humans
• Jurkat Cells
• Lung (metabolism)
• Mice, Inbred BALB C
• Polyethyleneimine (administration & dosage, chemistry)
• RNA, Small Interfering (administration & dosage)
• Receptors, Transferrin (metabolism)
• T-Lymphocytes (metabolism)
• Transferrin (administration & dosage, chemistry)