Virus-like particle-mediated intracellular delivery of mRNA cap analog with in vivo activity against hepatocellular carcinoma.

Zochowska, Monika; Piguet, Anne Christine; Jemielity, Jacek; Kowalska, Joanna; Szolajska, Ewa; Dufour, Jean-François; Chroboczek, Jadwiga (2015). Virus-like particle-mediated intracellular delivery of mRNA cap analog with in vivo activity against hepatocellular carcinoma. Nanomedicine : nanotechnology, biology, and medicine, 11(1), pp. 67-76. Elsevier 10.1016/j.nano.2014.07.009

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UNLABELLED 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. FROM THE CLINICAL EDITOR Adenovirus dodecahedron, a nanoparticulate proteinaceous biodegradable virus-like particle was used in this study as a vector for the concomitant delivery of cap structure analog and doxorubicine to hepatocellular carcinoma in a rat model, resulting in significant inhibition of tumor growth.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Piguet, Anne Christine and Dufour, Jean-François

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1549-9642

Publisher:

Elsevier

Language:

English

Submitter:

Lilian Karin Smith-Wirth

Date Deposited:

20 Apr 2015 10:12

Last Modified:

06 Nov 2015 09:37

Publisher DOI:

10.1016/j.nano.2014.07.009

PubMed ID:

25101883

Uncontrolled Keywords:

Adenoviral dodecahedron; Cap structure analogs; Doxorubicin; Drug delivery vector; Hepatocellular carcinoma; Oncogene eIF4E; Virus-like particle; eIF4E inhibitor

BORIS DOI:

10.7892/boris.67143

URI:

https://boris.unibe.ch/id/eprint/67143

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