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Gadolinium (Gd)-based contrast agents are extensively used for magnetic resonance imaging (MRI). Liposomes are potential nanocarrier-based biocompatible platforms for development of new generations of MRI diagnostics. Liposomes with Gd-complexes (Gd-lip) co-encapsulated with thrombolytic agents can serve both for imaging and treatment of various pathological states including stroke. In this study, we evaluated nanosafety of Gd-lip containing PE-DTPA chelating Gd +3 prepared by lipid film hydration method. We detected no cytotoxicity of Gd-lip in human liver cells including cancer HepG2, progenitor (non-differentiated) HepaRG, and differentiated HepaRG cells. Furthermore, no potential side effects of Gd-lip were found using a complex system including general biomarkers of toxicity, such as induction of early response genes, oxidative, heat shock and endoplasmic reticulum stress, DNA damage responses, induction of xenobiotic metabolizing enzymes, and changes in sphingolipid metabolism in differentiated HepaRG. Moreover, Gd-lip did not show pro-inflammatory effects, as assessed in an assay based on activation of inflammasome NLRP3 in a model of human macrophages, and release of eicosanoids from HepaRG cells. In conclusion, this in vitro study indicates potential in vivo safety of Gd-lip with respect to hepatotoxicity and immunopathology caused by inflammation.

In this study we tested the stimulatory effect of adamantylamide-l-alanyl-d-isoglutamine (AdDP) or its liposomal formulation (L-AdDP) on recovery of the granulocyte–macrophage hemopoietic progenitor cells in the bone marrow of sublethally irradiated mice of various ages. Number of GM-CFC progenitors in femur on day 10 was used as a parameter reflecting the stimulatory activity. Mice (aged 3–5 month) pre-treated with AdDP or L-AdDP via s.c. route displayed enhanced recovery of the granulocyte–macrophage hemopoietic progenitor cells at the dose of 5.5 Gy. Overaged mice (2 years) responded to the treatment when the dose was increased to 6.5 Gy, while radiation doses below 5.5 Gy should be used to see the stimulation effect in young mice (6 weeks). Entrapment of AdDP into liposomes enhanced costimulatory activity of sera of treated mice and prolongated this activity at least for 30 h after stimulation, in comparison to the mice treated with free AdDP where the costimulatory activity was spanned only up to 12 h. In conclusion, L-AdDP represents a suitable formulation of AdDP that induced recovery of GM-CFC progenitors in the femur of irradiated mice of various ages. The stimulatory effect depends on the extent of injury to bone marrow hemopoietic microenvironments caused by various doses of γ-irradiation. [Copyright &y& Elsevier]

Candida glabrata is a second most common human opportunistic pathogen which causes superficial but also life-threatening systemic candidosis. According to the localisation of mannans and mannoproteins in the outermost layer of the cell wall, mannan detection could be one of the first steps in the cell recognition of Candida cells by the host innate immune system. Mannans from the cell wall provide important immunomodulatory activities, comprising stimulation of cytokine production, induction of dendritic cells (DCs) maturation and T-cell immunity. The model of DCs represents a promising tool to study immunomodulatory interventions throughout the vaccine development. Activated DCs induce, activate and polarise T-cell responses by expression of distinct maturation markers and cytokines regulating the adaptive immune responses. In addition, they are uniquely adept at decoding the fungus-associated information and translate it in qualitatively different T helper responses. We find out, that C. glabrata mannan is able to induce proliferation of splenocytes and to increase the production of TNF-α and IL-4. Next, increased the expression of co-stimulatory molecules CD80 and CD86 and the proportion of CD4+CD25+ and CD4+CD28+ T cells during in vitro stimulation of splenocytes. Reported results provide C. glabrata mannan capability to modulate cytokine production, DCs activation and antigen presentation activity, influencing T-cell phenotype in response to stimulation. [ABSTRACT FROM AUTHOR]