title: Thioaptamer conjugated liposomes for tumor vasculature targeting.
abstract: Recent developments in multi-functional nanoparticles offer a great potential for targeted delivery of therapeutic compounds and imaging contrast agents to specific cell types, in turn, enhancing therapeutic effect and minimizing side effects. Despite the promise, site specific delivery carriers have not been translated into clinical reality. In this study, we have developed long circulating liposomes with the outer surface decorated with thioated oligonucleotide aptamer (thioaptamer) against E-selectin (ESTA) and evaluated the targeting efficacy and PK parameters. In vitro targeting studies using Human Umbilical Cord Vein Endothelial Cell (HUVEC) demonstrated efficient and rapid uptake of the ESTA conjugated liposomes (ESTA-lip). In vivo, the intravenous administration of ESTA-lip resulted in their accumulation at the tumor vasculature of breast tumor xenografts without shortening the circulation half-life. The study presented here represents an exemplary use of thioaptamer and liposome and opens the door to testing various combinations of thioaptamer and nanocarriers that can be constructed to target multiple cancer types and tumor components for delivery of both therapeutics and imaging agent.
authors.affiliation: Department of Nanomedicine, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, Texas 77030, USA.
authors.forename: Aman P
authors.initials: AP
authors.lastname: Mann
authors.forename: Rohan C
authors.initials: RC
authors.lastname: Bhavane
authors.forename: Anoma
authors.initials: A
authors.lastname: Somasunderam
authors.forename: Brenda
authors.initials: B
authors.lastname: Liz Montalvo-Ortiz
authors.forename: Ketan B
authors.initials: KB
authors.lastname: Ghaghada
authors.forename: David
authors.initials: D
authors.lastname: Volk
authors.forename: René
authors.initials: R
authors.lastname: Nieves-Alicea
authors.forename: K Stephen
authors.initials: KS
authors.lastname: Suh
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Ananth
authors.initials: A
authors.lastname: Annapragada
authors.forename: David G
authors.initials: DG
authors.lastname: Gorenstein
authors.forename: Takemi
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D002277:Carcinoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D002478:Cells, Cultured; D004337:Drug Carriers / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D008081:Liposomes; D013438:Sulfhydryl Compounds