Toxicity of Water-Soluble D-g-PNIPAM Polymers in a Complex with Chemotherapy Drugs and Mechanism of Their Action In Vitro

Author:

Prylutska Svitlana1,Grebinyk Anna23ORCID,Ponomarenko Stanislav4,Gövem Defne3,Chumachenko Vasyl4,Kutsevol Nataliya4ORCID,Petrovsky Mykola4,Ritter Uwe5ORCID,Frohme Marcus3ORCID,Piosik Jacek6ORCID,Prylutskyy Yuriy4

Affiliation:

1. Department of Plants Physiology, Biochemistry and Bioenergetics, National University of Life and Environmental Sciences of Ukraine, 03041 Kyiv, Ukraine

2. Deutsches Elektronen-Synchrotron DESY, Platanenallee 6, 15738 Zeuthen, Germany

3. Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, 15745 Wildau, Germany

4. Department of Biophysics and Neurobiology, Department of Chemistry, Taras Shevchenko National University of Kyiv, 01601 Kyiv, Ukraine

5. Institute of Chemistry and Biotechnology, Technical University of Ilmenau, 98693 Ilmenau, Germany

6. Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, 80-307 Gdańsk, Poland

Abstract

The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology–Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated.

Funder

Brandenburg program

Publisher

MDPI AG

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