title: 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.affiliation: Wayne State University, Detroit, MI, United States.
authors.forename: Yuran
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Wayne State University, Detroit, MI, United States.
authors.forename: Na Hyung
authors.initials: NH
authors.lastname: Kim
authors.affiliation: Wayne State University, Detroit, MI, United States.
authors.forename: Venkatareddy
authors.initials: V
authors.lastname: Nadithe
authors.affiliation: Wayne State University, Detroit, MI, United States; Karmanos Cancer Institute, Detroit, MI, United States.
authors.forename: Dana
authors.initials: D
authors.lastname: Schalk
authors.affiliation: Wayne State University, Detroit, MI, United States; Karmanos Cancer Institute, Detroit, MI, United States.
authors.forename: Archana
authors.initials: A
authors.lastname: Thakur
authors.affiliation: Philipps-Universität Marburg, Marburg, Germany.
authors.forename: Ayşe
authors.initials: A
authors.lastname: Kılıç
authors.affiliation: Wayne State University, Detroit, MI, United States; Karmanos Cancer Institute, Detroit, MI, United States.
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Lum
authors.affiliation: Wayne State University, Detroit, MI, United States.
authors.forename: David J P
authors.initials: DJP
authors.lastname: Bassett
authors.affiliation: Wayne State University, Detroit, MI, United States; Karmanos Cancer Institute, Detroit, MI, United States; Ludwig-Maximilians Universität München, Munich, Germany. Electronic address: Olivia.merkel@LMU.de.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Merkel
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000628:therapy*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D019169:Jurkat Cells; D008168:Lung / Q000378:metabolism; D008807:Mice, Inbred BALB C; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D011990:Receptors, Transferrin / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014168:Transferrin / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D014168:Transferrin; D011094:Polyethyleneimine; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: Asthma; Polyethylenimine (PEI); Pulmonary delivery; Transferrin; siRNA delivery