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Leukocytes and drug-resistant cancer cells are targets for intracellular delivery by adenoviral dodecahedron

Jedynak, M and Laurin, David and Dolega, Patryk and Podsiadla-Bialoskorska, M and Szurgot, Inga and Chroboczek, Jadwiga and Szolajska, Ewa (2018) Leukocytes and drug-resistant cancer cells are targets for intracellular delivery by adenoviral dodecahedron. Nanomedicine: Nanotechnology, Biology and Medicine, 14 (6). pp. 1853-1865. ISSN 15499634

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Official URL: http://doi.org/10.1016/j.nano.2018.05.001

Abstract

One of the major factors limiting the effectiveness of cancer chemotherapy is inefficient drug delivery. Systems enabling efficient delivery and enhanced intracellular uptake appear particularly promising in this respect. Virus-like particle, adenoviral dodecahedron (Dd), employs receptor-mediated endocytosis for cell penetration and is able to deliver intracellularly dozens of cargo molecules attached to one particle. We focused on studying Dd properties in the context of cancer treatment, showing that intratumoral injection of Dd, assessed in mouse xenograft model, results in vector accumulation in tumor without spreading in off-target organs. Moreover, we demonstrated that Dd is a promising vector targeting leukocytes and drug-resistant cancer cells. Dd uptake by human blood cells analyzed in vitro indicated the preference for leukocytes in comparison to red blood cells and platelets. Furthermore, internalization of Dd-doxorubicin conjugate by drug-resistant cells leads to increased nuclear accumulation of doxorubicin and significant enhancement of cytotoxicity against target cancer cells.

Item Type:Article
Subjects:Q Science > Q Science (General)
Divisions:Department of Protein Biosynthesis
ID Code:1610
Deposited By: M.Sc. Marta Jedynak
Deposited On:30 Jan 2019 13:46
Last Modified:19 May 2019 22:05

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