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Nanobiotechnology 2018
Page 43
Nano Research & Applications
ISSN: 2471-9838
E u r o S c i C o n C o n f e r e n c e o n
Nanotech & Nanobiotechnology
J u l y 1 2 - 1 3 , 2 0 1 8
P a r i s , F r a n c e
Virus-like particles (VLPs) are an attractive alternative to chemically synthesized nanoplatforms in development of novel
carriers for targeted drug delivery. Adenoviral dodecahedron (Ad Dd), the symmetrical, small (28 nm) and non-infectious VLP,
endowed with extraordinary ability for intracellular penetration through the receptor-mediated endocytosis followed by escape
from the endosomes before reaching lysosomes. This results in cytoplasmic delivery of cargo molecules in a functional form.
The chemical and genetic modifcations allow for covalent attachment of cargo molecules or their insertion into particle structure
without disrupting VLP integrity or penetration properties. The usefulness of Dd as a carrier for conjugated small molecules was
already proven by targeted delivery of anticancer agents to hepatocellular carcinoma tumor in animal model, leading to inhibition
of tumor growth. In the presented study we analysed delivery of doxorubicin conjugated to Dd (DdDOX). It was assessed in
multidrug-resistant (MDR) human uterine sarcoma MES-SA Dx5 cells. The results of cytotoxicity tests attested the ability of Dd
for circumvention of the Pglycoprotein 1 - mediated multidrug resistance mechanism. We demonstrated that effcient uptake of
Dd-DOX conjugate in MDR cells leads to accumulation of drug in cell nucleus and signifcantly enhances doxorubicin cytotoxicity
against target cancer cells. Furthermore, we demonstrated distinct Dd transduction effciency for white blood cells, that could
lead to the use of this vector for the transport of active molecules targeting leukocytes, in particular for in vitro testing of potential
anticancer agents intended to treat leukaemia. The suitability of Dd for such application is supported by the lack of cytotoxicity
of VLP in human peripheral blood mononuclear cells.
Images
The covalent attachment of doxorubicin to dodecahedron (Dd), enables effcient drug delivery and signifcantly enhances
cytotoxicity in multidrug resistant cancer cells in vitro. Importantly, the affnity of Dd in human blood ex vivo is highly in favor of
leukocytes, independently of their subtypes despite high representation of red blood cells and platelets. Thus, current results
demonstrate that Dd is a promising vector targeting leukocytes and drug resistant cancer cells
Leukocytes and drug-resistant cancer cells are targets for
intracellular delivery by adenoviral dodecahedron
Marta Jedynak 1, David Laurin2, Malgorzata Podsiadla-
Bialoskorska1 , Jadwiga Chroboczek1,3 and Ewa Szolajska1
1Institute of Biochemistry and Biophysics Polish Academy of Sciences, Poland
2Universite Grenoble Alpes, France
3Universite Grenoble Alpes, France
Biography
Ewa Szolajska (Ph. D) an Assistant Professor at Institute of Biochemistry and Biophysics Polish Academy of Sciences (IBB PAS) Warsaw, Poland, is a Group leader in the
Department of Protein Synthesis and Chief of Cell Culture Laboratory at IBB PAS. She got her Doctor’s degree and habilitation in Biochemistry from IBB PAS. Currently Dr. Ewa
Szolajskas’ research focus on the development of an adenovirus derived virus-like particle as an intracellular delivery vector for the therapeutic applications.
Ewa Szolajska et al., Nano Res Appl 2018, Volume 4
DOI: 10.21767/2471-9838-C2-012