Toxicity of Nanocomplexes Containing Gadolinium Orthovanadate Nanoparticles and Cholesterol.

Previous studies have shown the ability of nanocomplexes (NCs), which consist of nanoparticles (NPs) of orthovanadates of rare earth metals (GdYVO4:Eu3+) and cholesterol, to inhibit the growth of Ehrlich's ascites carcinoma (EAC). However, the biosafety of these NCs remains unclear. Our objective was to investigate the acute and subchronic toxicity of NCs. NCs were administered to BALB/c mice in NPs concentration of 5.9; 29.5; 59.1; and 118.2 mg/kg. Acute toxicity was induced by a single administration of NCs, subchronic-by repeated daily administration of NCs for 14 days. On day 15 and on day 31 for acute and subchronic toxicity, respectively, the percentage of animal survival, body weight, condition of visceral organs, and activities of γ-glutamyl transferase (GGT) and glucose-6-phosphate dehydrogenase (G-6-PDH) were determined. It was found that administration of NCs in the concentration of 5.9 mg/kg and 29.5 mg/kg of NPs did not influence on survival of animals or have a negative impact on their performance status, morphological and quantitative characteristics of visceral organs, and activities of the GGT and G-6-PDH in the liver. For acute toxicity, the semi-lethal dose (LD50) of nanocomplexes was determined (118.2 mg/kg of NPs). As to subchronic toxicity, it was found that repeated (for 14 days) administration of NCs containing 59.1 mg/kg of NPs decrease survival of animals to 50%. The coefficient of accumulation (Cacum = 7) indicates the low accumulative ability of NCs upon long-term use. Thus, from the LD50 and accumulation coefficient, NCs can be referred to as low-toxic substances and used in conditionally therapeutic doses in oncological practice to develop nanostructured formulations of drugs.

Cryoimmunology: Opportunities and challenges in biomedical science and practice.

Autologous and allogeneic cryoimmunological medicine is a brand new branch of biomedical science and clinical practice that examines the features and formation of the immune response to immunogenic properties of normal and malignant biological structures altered by ultralow temperature, as well as specific changes in the structural and functional characteristics of immune cells and tissues after cryopreservation. Cryogenic protein denaturation phenomenon provides important insights into the mechanisms underlying the damage to cryogenic lesions immediately after freeze-thawing sessions in bioscience and medicine applications. The newly formed cryocoagulated protein components (cryomodified protein components) are crucial in cryoimmunology from the perspective of the formation of immunological substances at ultralow temperatures. Dendritic cells and cryocell detritus (cryocell debris) formed in living biological tissue after exposure to ultralow temperature in vivo may be an indication of one of the essential mechanisms involved in the cryoimmunological response of living structures to the impact of ultralow temperature exposure. Hence, the formation of new autologous and allogeneic cryoinduced immunogenic substances is a novel concept in biomedical research globally. Accordingly, this review focuses on issues concerning the peculiarities of the interaction of the immune system with a dominant malignant neoplasm tissue after exposure to subzero temperatures, considering the original cryogenic technical approaches. We present an overview of the state-of-the-art methods of cryoimmunology, and their major developments, past and present. The need for the delineation of structural and functional characteristics of the biological substrates of the immune system after cryopreservation that can be used in adoptive cell therapy, especially in cancer patients, is emphasized.