New nanosized macro-molecular system and their interaction with biopolymers and living objects

Mikhail I. Shtilman*, Andrey Kuskov, Pavel P. Kulikov, Anna L. Luss, A.V. Goryachaya, V.T. Jedzheya, S.A. Gusev, P Heinrich-Noak, Leonid Gurevich, Vladimir Torchilin, Aristidis Tsatsakis


Publikation: Bidrag til tidsskriftKonferenceabstrakt i tidsskriftForskningpeer review


Methods of synthesis of amphiphilic derivatives of a number of watersoluble
polymers, in particular, poly-N-vinylpyrrolidone, have been
worked out. In experiments on cells and experimental animals, the
harmlessness of the polymers obtained was shown.
The synthesized amphiphilic polymers are capable of spontaneous
aggregation in aqueous solutions with the formation of nanoscale
micelle-like aggregates and are suitable for modifying liposomal
membranes. The influence of the structure of amphiphilic polymers
on the tendency to aggregation has been established. Such systems
can be used as carriers of poorly soluble and water-insoluble medicinal
substances [3,4].
It was shown, what aggregates of amphiphilic polymers of Nvinylpyrrolidone
proved to be suitable for use as carriers and modifiers
of various proteins and peptides (blood factor IX, angiostatin,
Bowman-Birk soybean proteinase inhibitor (BBI)). In these cases, immobilization
with the use of polymeric aggregates increases the
resistance of proteins to denaturing effects, and thereof their total
biological activity.
Methods have been developed for the introduction into the synthesized
amphiphilic polymers of various functional groups. For
example, introduction of additional side aminoacid groups in the
polymeric part of amphiphilic systems allows the use of aggregates
as carriers of nucleic acids and their subsequent application for transfection
in genetic engineering [5,6].
Using fluorescent labels and probes, it was shown that the immobilized
substance introduced into larger size aggregates penetrates
into the living cell due to endocytosis, localizing in the cytoplasm
inside the endosome. On the other hand, when immobilized
active agent is introduced in smaller-sized aggregates, it evenly
spreads both in the cytoplasm of the cell and in its nucleus. When
studying the transport of aggregates of amphiphilic polymers of Nvinylpyrrolidone
in the body (rats), it was established that a fluorescent
probe immobilized in aggregates of amphiphilic polymers, when
injected into the tail of experimental animals, quickly reaches the
vessels of the eye [7-9].
[1] V.P. Torchilin, M.I. Shtilman, V.S. Trubetskoy, K. Whiteman. Biochimica et
Biophysica Acta. Biomembranes N.1195, 181-184 (1994).
[2] V.P. Torchilin, T.S. Levchenko, K.R. Whiteman, A.A. Yaroslavov, Tsatsakis, A.M.,
A.K. Rizos, E.V. Michailova, M.I. Shtilman. Biomaterials. 22, 3035-3044 (2001).
[3] A.N. Kuskov, P.P. Kulikov, A.V. Goryachaya, M. Tzatzarakis, A.O. Docea, K.
Velonia, M.I. Shtilman, A.M.Tsatsakis. Nanomedicine: Nanotechnology, Biology,
and Medicine, 13, 1021-1030 (2017).
[4] A.N. Kuskov, P.P. Kulikov, A.V. Goryachaya, M.N. Tsatzarakis, A.M. Tsatsakis,
K.Velonia, M.I.Shtilman. J.of Applied Polymer Science 135, 45673 (2018).
[5] C.L. Andersen, S.B. Romme, P. Fojan, C.P. Pennisi, A.L. Luss, P.P. Kulikov,
L. Gurevich, M.I. Shtilman. Biophysical J. B511, 590 (2017).
6] A.L. Villemson, A.N. Kuskov, M.I., Shtilman, L.V. Galebskaya, E.V. Ryumina,
N.I. Larionova. Biochemistry (Moscow) 69, 765-775 (2004).
[7] O. Klimenko, M. Shtilman. Cancer Gene Therapy 20, 237-241 (2013).
[8] O. Klimenko, M. Shtilman. Food and Chem. Toxicol., (2019) (in press).
[9] A.L. Luss, C.L. Andersen, I.G. Benito, R.C. Marzo, Z.H. Medina, M.B. Rosenlund,
S.B. Romme, P.P. Kulikov, C.P. Pennisi, M.I. Shtilman, L. Gurevich.
Biophysical J.114, 278-279 (2018).
[10] A.L. Luss, P.P. Kulikov, S.B. Romme, C.L. Andersen, C.P. Pennisi, A.O. Docea,
A.N. Kuskov, K. Velonia, Ya.O. Mezhuev, M.I. Shtilman, A.M. Tsatsakis,
L. Gurevich. Nanosized carriers based on amphiphilic poly-N-vinyl-2-
pyrrolidone for intranuclear drug delivery. Nanomedicine, 13, 703-715 (2018).
[11] M. Tawfik, M. Sokolov, L. Grigartzik, P. Kulikov, A. Kuskov, M. Shtilman,
B.A. Sabel, P. Henrich-Noack. Bionanotox (Crete, Greece), P02 (2018).
TidsskriftToxicology Letters
Udgave nummerS1
Sider (fra-til)S45
Antal sider1
StatusUdgivet - 2019
Begivenhed55th Congress of the European Societies of Toxicology: Toxicology Science Providing Solutions - Helsinki, Finland
Varighed: 8 sep. 201911 sep. 2019


Konference55th Congress of the European Societies of Toxicology


Dyk ned i forskningsemnerne om 'New nanosized macro-molecular system and their interaction with biopolymers and living objects'. Sammen danner de et unikt fingeraftryk.