title: Tenfibgen ligand nanoencapsulation delivers bi-functional anti-CK2 RNAi oligomer to key sites for prostate cancer targeting using human xenograft tumors in mice.
abstract: Protected and specific delivery of nucleic acids to malignant cells remains a highly desirable approach for cancer therapy. Here we present data on the physical and chemical characteristics, mechanism of action, and pilot therapeutic efficacy of a tenfibgen (TBG)-shell nanocapsule technology for tumor-directed delivery of single stranded DNA/RNA chimeric oligomers targeting CK2αα' to xenograft tumors in mice. The sub-50 nm size TBG nanocapsule (s50-TBG) is a slightly negatively charged, uniform particle of 15 - 20 nm size which confers protection to the nucleic acid cargo. The DNA/RNA chimeric oligomer (RNAi-CK2) functions to decrease CK2αα' expression levels via both siRNA and antisense mechanisms. Systemic delivery of s50-TBG-RNAi-CK2 specifically targets malignant cells, including tumor cells in bone, and at low doses reduces size and CK2-related signals in orthotopic primary and metastatic xenograft prostate cancer tumors. In conclusion, the s50-TBG nanoencapsulation technology together with the chimeric oligomer targeting CK2αα' offer significant promise for systemic treatment of prostate malignancy.
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Janeen H
authors.initials: JH
authors.lastname: Trembley
authors.affiliation: GeneSegues Inc., Chaska, Minnesota, United States of America.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Unger
authors.affiliation: GeneSegues Inc., Chaska, Minnesota, United States of America.
authors.forename: Vicci L
authors.initials: VL
authors.lastname: Korman
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Md Joynal
authors.initials: MJ
authors.lastname: Abedin
authors.affiliation: GeneSegues Inc., Chaska, Minnesota, United States of America.
authors.forename: Lucas P
authors.initials: LP
authors.lastname: Nacusi
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Rachel I
authors.initials: RI
authors.lastname: Vogel
authors.affiliation: Department of Urology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Joel W
authors.initials: JW
authors.lastname: Slaton
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America; Department of Medicine, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Betsy T
authors.initials: BT
authors.lastname: Kren
authors.affiliation: Research Service, Minneapolis VA Health Care System, Minneapolis, Minnesota, United States of America; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, United States of America; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America; Department of Urology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Khalil
authors.initials: K
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D047390:Casein Kinase II / Q000235:genetics*; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D019063:Tenascin / Q000008:administration & dosage* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
chemical_list: D053769:Nanocapsules; D010446:Peptide Fragments; D034741:RNA, Small Interfering; D019063:Tenascin; C000597115:tenfibgen; D047390:Casein Kinase II