title: RNA nanoparticles harboring annexin A2 aptamer can target ovarian cancer for tumor-specific doxorubicin delivery.
abstract: A novel modified nucleic acid nanoparticle harboring an annexin A2 aptamer for ovarian cancer cell targeting and a GC rich sequence for doxorubicin loading is designed and constructed. The system utilizes a highly stable three-way junction (3WJ) motif from phi29 packaging RNA as a core structure. A phosphorothioate-modified DNA aptamer targeting annexin A2, Endo28, was conjugated to one arm of the 3WJ. The pRNA-3WJ motif retains correct folding of attached aptamer, keeping its functions intact. It is of significant utility for aptamer-mediated targeted delivery. The DNA/RNA hybrid nanoparticles remained intact after systemic injection in mice and strongly bound to tumors with little accumulation in healthy organs 6 h post-injection. The Endo28-3WJ-Sph1/Dox intercalates selectively enhanced toxicity to annexin A2 positive ovarian cancer cells in vitro. The constructed RNA/DNA hybrid nanoparticles can potentially enhance the therapeutic efficiency of doxorubicin at low doses for ovarian cancer treatment through annexin A2 targeted drug delivery.
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: Fengmei
authors.initials: F
authors.lastname: Pi
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA; Department of Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Diagnostic and Biomedical Sciences, University of Texas Health Science Center, Houston, TX, USA; AM Biotechnologies, Houston, TX, USA.
authors.forename: Varatharasa
authors.initials: V
authors.lastname: Thiviyanathan
authors.affiliation: Department of Diagnostic and Biomedical Sciences, University of Texas Health Science Center, Houston, TX, USA; AM Biotechnologies, Houston, TX, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Gorenstein
authors.affiliation: Department of Gynecologic Oncology and Center for RNA Interference and Non-Coding RNA, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, USA; Department of Physiology & Cell Biology, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA. Electronic address: guo.1091@osu.edu.
authors.forename: Peixuan
authors.initials: P
authors.lastname: Guo
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D017306:Annexin A2; D000903:Antibiotics, Antineoplastic; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D004317:Doxorubicin
keywords: Annexin A2; Aptamer; Doxorubicin; Ovarian cancer; RNA nanotechnology