Evaluation of the Immunosafety of Cucurbit[n]uril on Peripheral Blood Mononuclear Cells In Vitro

Abstract

Cucurbiturils (CB[n]s) are nanoscale macrocyclic compounds capable of encapsulating a molecule or part of a molecule by forming host–guest complexes. Integration of drugs with CB[n] is used for the following purposes: controlling clearance; protection of the drug from biodegradation; targeted delivery to specific organs, tissues, or cells; reduction of toxicity; and improving solubility. One of the major problems encountered in the application of new drug delivery systems is lack of knowledge of their biological properties. CB[n], unlike many other often toxic nanoparticles, has extremely low toxicity, even at high doses. However, many aspects of the biological actions of these nanoscale cavitands remain unclear, including the immunotropic properties. In this study, we investigated the immunotoxicity and immunomodulation properties of CB[n]. It was found that CB[7] and CB[6] did not decrease the viability of mononuclear cells at all tested concentrations from 0.1–1 mM. Overall, the results indicated an immunomodulatory effect of different concentrations of CB[n]. In the case of a longer cultivation time, CB[n] had an immunostimulating effect, which was indicated by an enhancement of the proliferative activity of cells and increased expression of HLA-DR on lymphocytes.

Influence of Cucurbiturils on the Production of Reactive Oxygen Species by T- and B-Lymphocytes, Platelets and Red Blood Cells

“…An important part of the discussion is the pathophysiological manifestations of the effect of CB-induced ROS variation on cell biological functions such as proliferation, apoptosis and hemolysis. We previously reported on the effect of cucurbit[n]urils on these processes [ 6 , 52 ], so we can make some assumption.…”

Overcoming barriers with non-covalent interactions: supramolecular recognition of adamantyl cucurbit[n]uril assemblies for medical applications

“…Furthermore, the results indicated an immunomodulatory effect of different concentrations of CB[n] and after a longer cultivation time CB[n] had an immunostimulating effect, which was indicated by an enhancement of the proliferative activity of cells and increased expression of HLA-DR on lymphocytes. 168 Since CB [7] has been the most studied representative of the CB[n] family in terms of potential biological application, biocompatibility and safety of CB [7] was systemically evaluated in vitro, ex vivo, and in vivo using animal and human cell lines, zebrafish and in mice. [162][163][164][165][166] It was shown in several in vivo studies that there is little or no obvious toxicity when the cell lines were treated with CB [7] at concentrations below 500 μM, 162,163 which is far above the concentrations typically needed for drug delivery.…”

“…Furthermore, the results indicated an immunomodulatory effect of different concentrations of CB[ n ] and after a longer cultivation time CB[ n ] had an immunostimulating effect, which was indicated by an enhancement of the proliferative activity of cells and increased expression of HLA-DR on lymphocytes. 168 …”

Effect of cucurbiturils on cytokine production by peripheral blood mononuclear cells of healthy donors

“…Russian Journal of Immunology/Rossiyskiy Immunologicheskiy Zhurnal Российский иммунологический журнал ного ответа. Ранее было продемонстрировано, что кукурбит [6]урил может способствовать увеличению экспрессии молекул HLA-DR на B-лимфоцитов [9], что также говорит о стимулирующем действии кукурбит [6]урила на гуморальное звено иммунитета. Кукурбит [7]урил не приводил к статистически значимым изменениям в спонтанной продукции МНК исследуемых цитокинов, однако была замечена тенденция (p = 0,09) по увеличению продукции провоспалительного цитокина TNF.…”