Virus-like particle-mediated intracellular delivery of mRNA cap analog with in vivo activity against hepatocellular carcinoma
| Autor: | Jean-François Dufour, Joanna Kowalska, Jadwiga Chroboczek, Anne Christine Piguet, Jacek Jemielity, Ewa Szolajska, Monika Zochowska |
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| Rok vydání: | 2015 |
| Předmět: |
Cytoplasm
Carcinoma Hepatocellular Genetic Vectors Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Antineoplastic Agents Bioengineering Biology Adenoviridae Proto-Oncogene Proteins c-myc In vivo Cell Line Tumor medicine Animals Humans General Materials Science Doxorubicin RNA Messenger Vaccines Virus-Like Particle Cell Proliferation Cell Nucleus Messenger RNA Oncogene Liver Neoplasms EIF4E medicine.disease Endocytosis Rats Eukaryotic Initiation Factor-4E Nanomedicine Hepatocellular carcinoma Cancer cell Cancer research Molecular Medicine Neoplasm Transplantation Intracellular HeLa Cells medicine.drug |
| Zdroj: | Nanomedicine: Nanotechnology, Biology and Medicine. 11:67-76 |
| ISSN: | 1549-9634 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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