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

Keywords: COVID-19; ascorbic acid; copper; fat-soluble vitamins; iron; magnesium; micronutrients; selenium; vitamin B complex; zinc..

In the current economic conditions, an active search is conducted for cost-effective and well-balanced feeds and feed mixtures for fish farming. The development of functional feeds using biomass of wild algae is becoming a central focus in the fish feed production. Although these supplements offer a promising path to sustainable and environmentally friendly fish feeding, their impact on the ecosystem requires detailed research. The aim of the study was to determine the acute response of Daphnia magna to the influence of new feed products derived from the  wild algae of the Baltic Sea, phycocyanin on its own, and their binary mixture. The study was conducted using the standard aquatic toxicology method. To establish the  48-hour LC50, the  probit analysis method was used. The results showed that D. magna is more sensitive to the effects of phycocyanin, with the following order of toxicity: phycocyanin > the mixture (1:1) > the biomass of Cladophora sp. The median lethal concentrations at 48 h were 100 mg/l, 920 mg/l, and 1720 mg/l, respectively. The obtained data allows to refer the tested compounds to low-hazard substances according to the Globally Harmonized System (GHS). The observed effects were compared with the effects of the mixture noticed in the toxic units (TU) model. In 48 hours, the mixture of the dry biomass of
Cladophora sp. and phycocyanin at a ratio of 1:1 exhibited synergism. The obtained results will allow choosing the optimal ratio of the raw materials used in fish feeds without inflicting harm to the aquatic ecosystem and loss of their nutritional value.

My interest in specific nanomaterials and nanobiotechnologies for biology and medicine started in 2005, when a couple of my colleagues who are organic and physical chemists sent me a proposal to investigate the biological activities of their products in order to evaluate the potential biomedical applications of the synthe-sized products. The role of my department at the Institute of Cell Biology, NAS of Ukraine, was to study the possibility of using new products, organic polymers and C60-fullerene nanoparticles, as platforms for drug and gene delivery. The need for such platforms exists because of the inaction of many medicines and their adverse effects in the treated organism. In addition, the physicochemical properties of many drugs, for example, with their poor water solubility, do not allow for a convenient application of these drugs. As a result of the realization of joint research projects with my colleagues working in Eastern and Central European countries, several nanoplatforms were developed for drug and gene delivery. Thus, there was a need
for the analysis and summarization of our experience in the molecular design, chemical synthesis, and biomedical application of novel nanomaterials in order to pass that experience to other scientists who work in this rapidly developing field of materials science. Most co-authors of this book participated in the TechConnect World Innovation Conference in Washington, DC (USA), in 2017. Their oral and poster presentations were visited by Merry Stuber, Senior Editor with Springer Nature Publishers. She asked Dr. Sandor Vari, Director of International Research and Innovation in Medicine Program (Cedars-Sinai Medical Center, Los Angeles, CA, USA) and RECOOP Association (https://www.cedars-sinai.org/research/administration/recoop.html), who managed our participation at the TechConnect World Innovation Conference, if he would prepare a book devoted to our results in the development of novel nanomaterials and nanobiotechnologies for biomedical use. This initiative was interrupted by COVID-19-related problems, but finally, we can present our
book to readers. The logistics of composing the presented materials is based on offering to read-ers a unique manual for their strategy for developing their own nanomaterials for biomedical applications, starting from their molecular design and synthesis, and moving to necessary steps of their physical-chemical and toxicological characteris-tics (biodegradability, biocompatibility, controlled delivery and clearance in the organism, as well as potential bio-risks for the environment). Both the organic (novel surface-active comb-like PEG-containing polymers) and mineral (novel water-soluble C60-fullerene-based nanoplatforms and magnetic iron oxide-based nano- and micro-particles for theranostics) materials used in biomedical applica-tions are described by the leading specialists in the corresponding fields. The nano-toxicology-related aspects of these and other biomedical materials are described
both in general, including genotoxicity and environmental toxicity, and specifically, hepato-, cardio-, nephro-, and immune-toxicities. Environmental aspects of the application of various nanomaterials have been characterized for freshwater and marine organisms, as well as for the multipollutant strategy of assessment of the environmental quality and health risks caused by air nano-pollutants. Bioimaging of nanomaterials is a central element for monitoring their biological action, and this aspect is described in the book as characterization of novel polymeric nanocarriers for gene delivery, which is a crucial step in gene therapy that is considered to be the future of medicine. The co-authors of all chapters of this book are thankful to the people who initi-
ated its writing, as well as to numerous members of the research teams who assisted in the experiments aimed at the development of novel nanomaterials and nanobio-technologies for biomedical applications.