title: Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice.
abstract: The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions.
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Shin-Ae
authors.initials: SA
authors.lastname: Kang
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Bilegtsaikhan
authors.initials: B
authors.lastname: Tsolmon
authors.affiliation: Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, United States.
authors.forename: Aman P
authors.initials: AP
authors.lastname: Mann
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Lichao
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Yan Daniel
authors.initials: YD
authors.lastname: Zhao
authors.affiliation: Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Volk
authors.affiliation: Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, United States.
authors.forename: Ganesh L-R
authors.initials: GL
authors.lastname: Lokesh
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Lynsie
authors.initials: L
authors.lastname: Morris
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Vineet
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States.
authors.forename: Wajeeha
authors.initials: W
authors.lastname: Razaq
authors.affiliation: Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107, United States.
authors.forename: Hallgeir
authors.initials: H
authors.lastname: Rui
authors.affiliation: John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601, United States.
authors.forename: K Stephen
authors.initials: KS
authors.lastname: Suh
authors.affiliation: Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030, United States.
authors.forename: David G
authors.initials: DG
authors.lastname: Gorenstein
authors.affiliation: Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104, United States. Electronic address: takemi-tanaka@ouhsc.edu.
authors.forename: Takemi
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000473:pathology; D015926:Complement C3a / Q000378:metabolism; D015936:Complement C5a / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019040:E-Selectin / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D009336:Necrosis; D018570:Risk Assessment
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D015415:Biomarkers; D016207:Cytokines; D019040:E-Selectin; D015926:Complement C3a; D015936:Complement C5a; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: E-selectin; Mono-thioated aptamer; Safety; Systemic toxicity