А series of the work "Delivery of genetic material and drugs into eukaryotic cells by nanocarriers"

Work number - M 28 AWARDED

Authors:Burlaka O.M., Riabtseva A.О., Senkiv J.V., Finiuk N.S.

Presented by the Institute of Food Biotechnology and Genomics, National Academy of Sciences of Ukraine

The cycle of scientific works consists of 1 chapter in monograph and 20 scientific articles published during the 2010-2104.

The background of the exploiting various nanocarriers for the delivery of genetic material and drugs into eukaryotic cells is developed. The strategy for the synthesis of functional polymers with side polyethylene glycol (PEG) and polyelectrolyte chains is proposed. Mechanisms of the polymer-analogous transformations involving epoxy and peroxide fragments of epoxide-containing polyperoxides were studied. Novel water-soluble comb-like polymer surfactants combining PEG and polyelectrolyte chains are developed. The possibility of  binding anticancer agents as well as genes to carriers with subsequent formation of nano- and micro-sized water delivery systems is shown. High efficiency of the polymer carriers for the nanoscale anticancer drug delivery systems development is reported. It was shown that new polymeric-phospholipidic hybrid delivery system distinctly enhanced the accumulation and activity of doxorubicin (Dox) in all tested cancer cell lines. Moreover, the new nanocarriers were able to transport Dox into cancer cells rapidly and effectively. The basic mechanisms of cellular uptake are studied for these complexes, and ways to improve the effectiveness of their in vitro and in vivo activity are developed.

For the first time the study of delivery of genes into mammalian cells of different lines (NEK293T, MCF-7, HeLa, HCT-116, L929, MDA-MB-231, SK-MEL-28) in vitro by novel polymeric carriers based on poly-DMAEM is reported. It was shown that use of novel polymers provides the increase in p21 and p53 proteins expression in mammalian cells. This observation is important for the further implementation of the results in the practice of gene therapy. Low toxicity and lack of mutagenic effect of synthesized polymeric DNA carriers is demonstrated. The background for the exploiting of single- and multi-walled carbon nanotubes (CNTs) as DNA delivery vectors for plant cells is developed. Novel method for the non-covalent functionalization for efficient dispersing of CNTs in water environments and further use in plant biotechnology is proposed. Genetic transformation of mesophyll protoplasts, callus and leaf explants of tobacco Nicotiana tabacum L.  mediated by CNT-DNA complexes is conducted and better suitability of single-walled CNTs for the exploiting for transformation of plants is shown.

The results of the cycle are important to clarify the basic mechanisms and improve the existing methods of drug and gene delivery into eukaryotic cells.

The results of studies on the subject are set out in 1 chapter in monograph, 20 articles (including 5 in foreign journals), 1 information brochure and 56 abstracts. Works of authors cited in more than 20 scientific journals, general citation index of the publications is 6 (according to the Scopus database), h-index = 5.Total number of publications of authors is 78.