Purpose: Our study aimed to assess the effects of anticancer 4-thiazolidinone-based free water-insoluble therapeutics Les-3288 and
Les-3833 and their waterborne complexes with branched PEG-containing polymeric carriers (A24-PEG550 and A24-PEG750) on
immune response.
Methods: Human peripheral blood was used to study in vitro lymphocyte proliferative function, leukocyte phagocytic activity and
respiratory burst, and cytokine production.
Results: The binding of the polymer to the anticancer drug Les-3288, which is intended to mitigate the immunosuppressive effects of the
free drug on the proliferative activity of T lymphocytes and T-dependent B cells, demonstrated comparable efficacy for both A24-PEG750
and A24-PEG550 nanocarriers. Furthermore, it was observed that the drug-polymer complex significantly increased the reduced levels of
IFN-γ and TNF-α resulting from free Les-3288. Conversely, the reduced levels of IL-6 and IL-4 remained unchanged. Administration of
either form of Les-3288 had no effect on the phagocytic activity of monocytes, granulocytes or the respiratory burst of granulocytes. Due to
the reduced cell viability and increased cytotoxicity associated with Les-3833, tenfold lower doses were selected for the immune assays.
The effects of free Les-3833 on lymphocyte proliferative function resulted in significant stimulation of T-dependent B cells. The binding of
Les-3833 to the smaller carrier, A24-PEG550 was found to maintain the stimulatory effect on B lymphocytes. While no effect of free Les3833 on the granulocyte phagocytic activity was observed, binding of Les-3833 to both polymeric carriers resulted in a decrease in
granulocyte phagocytic activity and respiratory burst, with no observable effect on monocytes. Monitoring of cytokine production showed
no significant effect of either form of Les-3833 on the production of IFN-γ and IL-6. In the context of TNF-α and IL-4, the positive effect of
polymer binding on restoring suppressed cytokine levels induced by the Les-3833 free drug was slightly more favorable for A24-PEG750.
Conclusion: The drug complexation with novel PEGylated carriers is a promising way for efficient therapeutic development.
Keywords: anticancer compounds, lymphocytes, phagocytic activity, respiratory burst, cytokines