title: CK2 Molecular Targeting-Tumor Cell-Specific Delivery of RNAi in Various Models of Cancer.
abstract: Protein kinase CK2 demonstrates increased protein expression relative to non-transformed cells in the majority of cancers that have been examined. The elevated levels of CK2 are involved in promoting not only continued proliferation of cancer cells but also their resistance to cell death; thus, CK2 has emerged as a plausible target for cancer therapy. Our focus has been to target CK2 catalytic subunits at the molecular level using RNA interference (RNAi) strategies to achieve their downregulation. The delivery of oligonucleotide therapeutic agents warrants that they are protected and are delivered specifically to cancer cells. The latter is particularly important since CK2 is a ubiquitous signal that is essential for survival. To achieve these goals, we have developed a nanocapsule that has the properties of delivering an anti-CK2 RNAi therapeutic cargo, in a protected manner, specifically to cancer cells. Tenfibgen (TBG) is used as the ligand to target tenascin-C receptors, which are elevated in cancer cells. This strategy is effective for inhibiting growth and inducing death in several types of xenograft tumors, and the nanocapsule elicits no safety concerns in animals. Further investigation of this therapeutic approach for its translation is warranted.
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA. trem0005@umn.edu.|Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. trem0005@umn.edu.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. trem0005@umn.edu.
authors.forename: Janeen H
authors.initials: JH
authors.lastname: Trembley
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA. krenx@umn.edu.|Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. krenx@umn.edu.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. krenx@umn.edu.
authors.forename: Betsy T
authors.initials: BT
authors.lastname: Kren
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA. mdjoynal@yahoo.com.|Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. mdjoynal@yahoo.com.
authors.forename: Md Joynal
authors.initials: MJ
authors.lastname: Abedin
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. isak0023@umn.edu.|Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, MN 55455, USA. isak0023@umn.edu.
authors.forename: Rachel I
authors.initials: RI
authors.lastname: Vogel
authors.affiliation: School of Veterinary Medicine, University of Minnesota, Minneapolis, MN 55455, USA. clairemcannon@gmail.com.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Cannon
authors.affiliation: GeneSegues Therapeutics, Minnetonka, MN 55343, USA. gmu@genesegues.com.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Unger
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA. ahmedk@umn.edu.|Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. ahmedk@umn.edu.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. ahmedk@umn.edu.|Department of Urology, University of Minnesota, Minneapolis, MN 55455, USA. ahmedk@umn.edu.
authors.forename: Khalil
authors.initials: K
authors.lastname: Ahmed
keywords: CK2; HNSCC; RNAi; TBG; TBG-RNAi-CK2; anti-CK2; breast cancer; cancer; cancer-specific; nanocapsules; nanoparticles; prostate cancer; siRNA; targeting; tenfibgen; therapy; tumor-specific