PMID- 25101883 OWN - NLM STAT- MEDLINE DCOM- 20150804 LR - 20141229 IS - 1549-9642 (Electronic) IS - 1549-9634 (Linking) VI - 11 IP - 1 DP - 2015 Jan TI - Virus-like particle-mediated intracellular delivery of mRNA cap analog with in vivo activity against hepatocellular carcinoma. PG - 67-76 LID - S1549-9634(14)00419-5 [pii] LID - 10.1016/j.nano.2014.07.009 [doi] AB - Adenovirus dodecahedron (Dd), a nanoparticulate proteinaceous biodegradable virus-like particle (VLP), was used as a vector for delivery of an oncogene inhibitor to hepatocellular carcinoma (HCC) rat orthotopic model. Initiation factor eIF4E is an oncogene with elevated expression in human cancers. Cell-impermeant eIF4E inhibitor, cap structure analog (cap) and anti-cancer antibiotic doxorubicin (Dox) were delivered as Dd conjugates. Dd-cap and Dd-dox inhibited cancer cell culture proliferation up to 50 and 84%, respectively, while with free Dox similar results could be obtained only at a 5 times higher concentration. In animal HCC model the combination treatment of Dd-cap/Dd-dox caused 40% inhibition of tumor growth. Importantly, the level of two pro-oncogenes, eIF4E and c-myc, was significantly diminished in tumor sections of treated rats. Attachment to Dd, a virus-like particle, permitted the first demonstration of cap analog intracellular delivery and resulted in improved doxorubicin delivery leading to statistically significant inhibition of HCC tumor growth. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Zochowska, Monika AU - Zochowska M AD - Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland. FAU - Piguet, Anne-Christine AU - Piguet AC AD - Hepatology, Department of Clinical Research, University of Berne, Berne, Switzerland. FAU - Jemielity, Jacek AU - Jemielity J AD - Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, Poland; Centre of New Technologies, University of Warsaw, Warsaw, Poland. FAU - Kowalska, Joanna AU - Kowalska J AD - Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Warsaw, Poland. FAU - Szolajska, Ewa AU - Szolajska E AD - Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland. FAU - Dufour, Jean-Francois AU - Dufour JF AD - University Clinics of Visceral Surgery and Medicine, Inselspital Berne, Berne, Switzerland. FAU - Chroboczek, Jadwiga AU - Chroboczek J AD - Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland; Therex, TIMC-IMAG, CNRS, Universite Joseph Fourier, La Tronche, France. Electronic address: jadwiga.chroboczek@imag.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140805 PL - United States TA - Nanomedicine JT - Nanomedicine : nanotechnology, biology, and medicine JID - 101233142 RN - 0 (Antineoplastic Agents) RN - 0 (Eukaryotic Initiation Factor-4E) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 0 (RNA, Messenger) RN - 0 (Vaccines, Virus-Like Particle) RN - 80168379AG (Doxorubicin) SB - IM MH - Adenoviridae/metabolism MH - Animals MH - Antineoplastic Agents/chemistry MH - Carcinoma, Hepatocellular/*therapy MH - Cell Line, Tumor MH - Cell Nucleus/metabolism MH - Cell Proliferation MH - Cytoplasm/metabolism MH - Doxorubicin/chemistry MH - Endocytosis MH - Eukaryotic Initiation Factor-4E/*metabolism MH - Genetic Vectors MH - HeLa Cells MH - Humans MH - Liver Neoplasms/*therapy MH - Nanomedicine/methods MH - Neoplasm Transplantation MH - Proto-Oncogene Proteins c-myc/metabolism MH - RNA, Messenger/*metabolism MH - Rats MH - Vaccines, Virus-Like Particle/*pharmacology OTO - NOTNLM OT - Adenoviral dodecahedron OT - Cap structure analogs OT - Doxorubicin OT - Drug delivery vector OT - Hepatocellular carcinoma OT - Oncogene eIF4E OT - Virus-like particle OT - eIF4E inhibitor EDAT- 2014/08/08 06:00 MHDA- 2015/08/05 06:00 CRDT- 2014/08/08 06:00 PHST- 2013/11/06 00:00 [received] PHST- 2014/06/17 00:00 [revised] PHST- 2014/07/23 00:00 [accepted] PHST- 2014/08/08 06:00 [entrez] PHST- 2014/08/08 06:00 [pubmed] PHST- 2015/08/05 06:00 [medline] AID - S1549-9634(14)00419-5 [pii] AID - 10.1016/j.nano.2014.07.009 [doi] PST - ppublish SO - Nanomedicine. 2015 Jan;11(1):67-76. doi: 10.1016/j.nano.2014.07.009. Epub 2014 Aug 5.