Nanobiotechnology and Cancer Research
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Інститут молекулярної біології і генетики НАН України
2012
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irk-123456789-1568612019-06-20T01:27:04Z Nanobiotechnology and Cancer Research Abstracts of Research Networks’ Young Scientist Forum 2012 Article Nanobiotechnology and Cancer Research // Вiopolymers and Cell. — 2012. — Т. 28, № 2, доп. — С. 77-80. — англ. 0233-7657 http://dspace.nbuv.gov.ua/handle/123456789/156861 en Вiopolymers and Cell Інститут молекулярної біології і генетики НАН України |
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Abstracts of Research Networks’ Young Scientist Forum Abstracts of Research Networks’ Young Scientist Forum |
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Abstracts of Research Networks’ Young Scientist Forum Abstracts of Research Networks’ Young Scientist Forum Nanobiotechnology and Cancer Research Вiopolymers and Cell |
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Nanobiotechnology and Cancer Research |
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Nanobiotechnology and Cancer Research |
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Nanobiotechnology and Cancer Research |
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Nanobiotechnology and Cancer Research |
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Nanobiotechnology and Cancer Research |
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nanobiotechnology and cancer research |
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Інститут молекулярної біології і генетики НАН України |
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Nanobiotechnology and Cancer
Research // Вiopolymers and Cell. — 2012. — Т. 28, № 2, доп. — С. 77-80. — англ. |
| series |
Вiopolymers and Cell |
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2025-07-14T09:10:52Z |
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2025-07-14T09:10:52Z |
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1837612927969918976 |
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77
Nanobiotechnology and Cancer
Research
78
Bio-application of novel non-viral gene delivery nanocarrier
1,2Finiuk N., 2Vitak T., 1Filyak Y., 3Mitina N., 3Zaichenko O., 1Stoika R.
1 Institute of Cell Biology, Drahomanov St.
14/16, 79005, Lviv, Ukraine
2 Ivan Franko National University of Lviv,
Hrushevskyi St., 4, 79005, Lviv, Ukraine
3 Lviv National Polytechnic University,
9 St. Yura Sq., 79013 Lviv, Ukraine
nataliyafiniuk@gmail.com
Gene delivery holds great potential in treatment of genetic and acquired human diseases.
The success of non-viral gene therapy has been limited by inefficient gene delivery due
to the presence of biological barriers for gene transfer, as well as high toxicity and
immunogenicity.
Aim: Characteristics of highly efficient, safe, non-toxic, non-immunogenic gene delivery
based on using novel olygoelectrolyte nanosized polymers.
Methods: Novel comb-like oligoelectrolyte nanocarriers were synthesized at Lviv
National Polytechnic University via controlled radical copolymerization using
oligoperoxide Cu+2 coordinating complexes. Electrophoresis, turbidimetry, MTT assay,
Ames mutagenicity test were used. Transfection efficiency was determined by
monitoring Green Fluorescent Protein expression.
Results: DNA-binding capacity of the polymers was evaluated and the best ones were tested for gene
delivery. Transfection conditions were optimized. It was found that BG-2 oligoelectrolyte
possessed 5-7 times higher gene delivery efficiency than other classical transfection
methods. BG-2 was efficient in crossing cellular barriers due to high lipophilic activity
and forming stable and small sized complexes with DNA. We observed that DNA was
completely protected by BG-2 from the action of nucleases. The nanocarrier
demonstrated low cytotoxicity and no mutagenic potencial towards treated cells.
Conclusions: Novel DMAEM-based olygoelectrolyte nanosized polymers are
perspective for the use as nonviral gene delivery vectors. They are non-toxic and non-
mutagenic. Their application is handy and time saving.
Keywords: Nonviral gene delivery, oligoelectrolyte polymeric nanocarrier.
This work was partially supported by CRDF and WUBMRC grants.
79
PDMAAm-coated -Fe2O3 nanoparticles for cell labeling
Zasońska B. A., 1Boiko N.b, Horák D., 1Stoika R.
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic,
Heyrovského Sq. 2, 162 06 Prague, Czech Republic;
1Institute of Cell Biology NASU,
14/16, Dragomanov St. 79005 Lviv, Ukraine
zasonska@imc.cas.cz
Aim: Synthesis of poly(N,N′-dimethylacrylamide) (PDMAAm)-coated -Fe2O3 core-shell
nanoparticles (NPs) by „grafting from” method and their use for mammalian cell labeling.
Methods: Superparamagnetic maghemite (-Fe2O3) nanoparticles were synthesized by co-
precipitation of FeCl2 and FeCl3 with ammonium hydroxide that was followed by oxidation of
magnetite with sodium hypochlorite. Surface of -Fe2O3 nanoparticles was functionalized by
three different initiators [2,2'–azobis (2-methylpropionamidine) dihydrochloride, 4-cyano-4-{[2-
cyano-3-(N-hydroxycarbamoyl)-2-methylpropyl]azo}pentanoic acid and 2,2'-azobis(N'-hydroxy-
2-methylpropanimidamide)]. “Grafting-from” method was then applied for the attachment of
PDMAAm on the NP surface. Both uncoated and PDMAAm-coated -Fe2O3 nanoparticles were
thoroughly characterized by scanning and transmission electron microscopy, Fourier-transform
infrared spectroscopy (FT-IR), dynamic light scattering, zetasizer, and elemental analysis.
Murine macrophages of J774.2 line were used as a model to investigate the engulfment of the
NPs by the cells using light and fluorescence microscopy. Cytotoxicity of the NPs was also
determined.
Results: Maghemite NPs ( 9 nm) with a rather narrow size distribution (characterized by
polydispersity index = 1.24) were synthesized by wet co-precipitation method and oxidation.
Surface of the -Fe2O3 nanoparticles was functionalized with different initiators whose presence
was confirmed by FT-IR spectroscopy. Properties of the NPs did not change substantially after
the functionalization. Further polymerization produced PDMAAm-coated -Fe2O3 nanoparticles.
While their size in dry state increased to 13-16 nm, the hydrodynamic diameter was also higher
(200 nm) compared with that of the uncoated NPs (113 nm). The NPs formed a stable colloid in
aqueous solutions, as documented by the zeta–potential equal -51 mV. PDMAAm-coated -
Fe2O3 nanoparticles were then investigated in the in vitro cell experiments in terms of their
engulfment by murine macrophages at 30 min, 1 h, 2 h, 3 h, or 24 h of cell culturing. The NPs
were relatively non-toxic for the cultured cells. Their engulfment was very efficient and already
after 3 h treatment, a majority of PDMAAm-γ-Fe2O3 nanoparticles was engulfed by the
macrophages. Effect of the mode of NP modification on cell engulfment is discussed.
Conclusions: Superparamagnetic NPs were successfully prepared by co-precipitation, and they
were coated with PDMAAm using „grafting-from” the initiator-functionalized particle approach.
The PDMAAm γ-Fe2O3 nanoparticles formed a stable aqueous colloid. Cell experiments proved
that the NPs were not cytotoxic. The PDMAAm--Fe2O3 nanoparticles were very quickly
engulfed by murine macrophages of J774.2 line. Thus, they show high potential for use in
diagnostics of phagocytic activity. Delivery of various significant biomedical substances, e.g.,
specific proteins and medicines, by using such NPs can be also anticipated.
Supported by GA CR P206/12/0381.
80
Structure-activity relationships of landomycins
1Panchuk R. R., 1,2Lehka L. V., 3Shaaban Kh. M., 3Rohr J., 2Ostash B. O.,
2Fedorenko V. O., 1,2Stoika R. S.
1Institute of Cell Biology NASU,
79005, Lviv, Drahomanov Str 14/16
2Ivan Franko Lviv National University, Biology Faculty,
79005, Lviv, Hrushevskogo Str 4
3University of Kentucky, College of Pharmacy,
789 S. Limestone St. Lexington
rpanchuk@ukr.net
Aim: In-depth study of molecular mechanisms of anticancer activity of 7 members of
landomycin (L) family (LA, 11-deoxyLA, LB, 11-deoxyLB, LE, LD, 11-deoxyLD), and
identification of key motifs in chemical structure that are responsible for their
antineoplastic potential.
Methods: Annexin V/propidium iodide staining – for quantitative measurement of
apoptotic/necrotic cells, DAPI staining – for qualitative analysis of chromatin
fragmentation, Western-blot analysis and flow cytometry – for cell cycle measurement,
caspase inhibition assays and Western-blot analysis on a panel of 20 proteins involved in
apoptosis – for identification of molecular targets of Ls in target cells.
Results: We found that elimination of C11-OH group in the aglycon structure
significantly decreased anticancer potential of Ls, and the most drastic difference was
observed with Ls with 6 sugar residues: while the IC50 of LA is 0.3 µM, the IC50 of 11-
deoxy LA is only 3 µM. All Ls with 11-OH group at the aglycon specifically blocked
tumor cell progression in G1 phase, in contrast to chemically related anticancer drug
doxorubicin which caused G2/M block. L-induced G1-block was p21- and p27-
dependent. Deoxy Ls did not possess such specificity. The activation of effector caspase-
7 and cleavage of its substrate PARP-1 took place already in 3 h after starting LE
treatment of Jurkat T-leukemia cells, while activation of the initiator caspases-2, -8, -9,-
10 and mitochondrial proteins Bid, Bax, AIF, Cytochrome C took place much later – 9-
12 h. We did not find any significant activation of caspase-3 in tumor cells by LE, while
doxorubicin activated it.
Conclusions: Key structures in the molecule of landomycins responsible for their
anticancer activity are three or more saccharide residues in glycosidic chain, mandatory
terminal residue of L-rhodinose, and presence of C11-OH group in aglycon part. Effector
caspase-7 is a potential target of landomycins. Such targeting might allow these drugs
effectively killing tumor cells defective on other apoptotic proteins and, thus, resistant to
chemotherapy.
Keywords: landomycins, tumor chemotherapy, apoptosis, caspases
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