Nanobiotechnology for health-care
Temperature-responsive smart nanocarriers for delivery of anticancer drugs: recent advances and disadvantages

Kutsevol N.V.1, Harahuts Yu.I.1,  Naumenko A.P.1, Chekhun V.F.2, 
  
E-mail: kutsevol@ukr.net
1Taras Shevchenko National University of Kyiv, Volodymyrska, 60, Kyiv 01601. 
2R.E. Kavetsky Institute for Experimental Pathology, Oncology and Radiobiology, Vasilkivska, 45, Kyiv 03022.

Water-soluble polymers with special characteristics can be used therapeutically as drug carriers in which the active ingredient are entrapped, encapsulated, adsorbed or chemically attached. The thermosensitive star-like  Dextran-graft-Poly-N-isopropyacrylamide copolymer was used as a matrix for synthesis of nanocomposites for photodynamic therapy. This polymer has LCST (33,4˚C) in the region of physiological temperatures. The nanosystems were characterized by DLS and UV-vis at 25 and 37˚ C and tested in vitro for their photodynamic anticancer activity. The understanding of the processes occurring during the formation of multicomponent nanosystem consisting of polymer nanocarrier, gold nanoparticles (AuNPs) and photosensitizer Chlorine e6 (Ce6) is the urgent tasks for synthesis of antitumor nanocomposites. 
It was shown that in Hank's saline solution at 25 °C D-PNIPAA/AuNPs and D-PNIPAA/AuNPs/Ce6 nanosystems didn’t not undergo drastic changes in compared to the same systems in water. Just a slight compactification of the macromolecular coil registered. It was found that an aggregation process become more evident at the presence of Ce6. At 37° C the size of AuNPs does not change, but a compactification of aggregates of macromolecules took place. 
	In vitro testing of photodynamic activity of D-PNIPAA/AuNPs/Ce6 nanosystems on the culture MT-4 of malignified lymphocytes of human showed that after laser irradiation the death of cells incubated with nanocomposite was only 4% higher than the cells incubated with free Ce6 of the same concentration. Thus, the aggregation processes, as well as the compactification of the polymer nanocarrier after LCST leaded to decreasing of the photosensitizer activity.
Acknowledgment
This publication is supported in part by the Ministry of the Education and Science of Ukraine: joint Ukrainian-Belarusian research and development projects “Design and physicochemical properties of new multicomponent nanosystems for treatment and diagnosis of solid tumors” (2019-2020).