Silver nanoparticles induce a non-immunogenic tumor cell death.

Immunogenic cell death (ICD) is a form of cell death characterized by the release of danger signals required to trigger an adaptive immune response against tumor-associated antigens. Silver nanoparticles (AgNP) display anti-proliferative and cytotoxic effects in tumor cells, but it has not been previously studied whether AgNP act as an ICD inductor. The present study evaluated the in vitro release of calreticulin as a damage-associated molecular pattern (DAMP) associated with the cytotoxicity of AgNP and their in vivo anti-cancer effects. In vitro, mouse CT26 colon carcinoma and MCA205 fibrosarcoma cells were exposed to AgNP and then cell proliferation, adhesion, and release of calreticulin were determined. The results indicated there were time- and concentration-related anti-proliferative effects of AgNP in both the CT26 and MCA205 lines. Concurrently, changes in cell adhesion were detected mainly in the CT26 cells. Regarding DAMP detection, a significant increase in calreticulin was observed only in CT26 cells treated with doxorubicin and AgNP; however, no differences were found in the MCA205 cells. In vivo, the survival and growth of subcutaneous tumors were monitored after vaccination of mice with cell debris from tumor cells treated with AgNP or after intra-tumoral administration of AgNP to established tumors. Consequently, anti-tumoral prophylactic immunization with AgNP-dead cells failed to protect mice from tumor re-challenge; intra-tumor injection of AgNP did not induce a significant effect. In conclusion, there was a noticeable anti-tumoral effect of AgNP in vitro in both CT26 and MCA205 cell lines, accompanied by the release of calreticulin in CT26 cells. In vivo, immunization with cell debris derived from AgNP-treated tumor cells failed to induce a protective immune response in the cancer model mice. Clearly, further research is needed to determine if one could combine AgNP with other ICD inducers to improve the anti-tumor effect of these nanoparticles in vivo.

Toxicity of silver nanoparticles in mouse bone marrow-derived dendritic cells: Implications for phenotype.

Silver nanoparticles (AgNP) are one of the most studied nanoparticles due to their anti-bacterial, -fungal, -viral, -parasitic, and -inflammatory properties. This raises the need to evaluate the toxicity and biological effects of AgNP in the immune system in order to develop new safer biomedical products. In this study, an AgNP formulation currently approved for veterinary applications was applied to mouse bone marrow-derived dendritic cells (BMDC), considered important antigen-presenting cells of the immune system, to evaluate cytotoxicity, genotoxicity, and any significant influence on expression of cellular markers associated with BMDC phenotype and maturation status. The results showed that after 12 h of AgNP exposure, a significant decrease in BMDC viability occurred at the highest concentration tested (1.0 µg AgNP/ml) and at lower doses, the cells maintained membrane integrity and metabolic activity. DNA damage was not significant with any AgNP level aside from the 1.0 µg AgNP/ml level. Regarding phenotype, no differences in expression of CD40 (co-stimulatory molecule highly present in mature BMDC) or in CD273 (a marker for inhibitory T-cell response) were observed. The current results showed that the toxicity of this AgNP formulation was dose-related. The findings also suggest BMDC could maintain structural conservation of co-stimulatory/co-inhibitory surface molecules after 12 h of exposure to this AgNP. This work represents the first step in identifying the toxic effects of this AgNP formulation on dendritic cells.

Effect of the ADIPOQ Gene -11391G/A Polymorphism Is Modulated by Lifestyle Factors in Mexican Subjects.

BACKGROUND/AIMS: Single nucleotide polymorphisms (SNPs) in the ADIPOQ gene could explain the adiponectin level. However, the knowledge about the influence of genetic and lifestyle factors is not sufficient. The aim was to analyze whether the effect of the -11391G/A SNP in the ADIPOQ gene is modulated by lifestyle factors in Mexican subjects. METHODS: A cross-sectional study was performed in which 394 participants were analyzed. Genetic, anthropometric, biochemical, dietary, clinical and physical activity parameters were measured. Statistical analysis was performed with SPSSv19 software. RESULTS: The distribution of the -11391G/A SNP genotypes was 55.6 and 44.4% for GG and AG, respectively. The adiponectin level was modulated by the -11391G/A SNP in response to the body mass index (BMI); A allele carriers showed a higher adiponectin level compared to G homozygous carriers but only in the minor BMI tertile group (p=0.032). Adiponectin level variability was explained by gender [(r)=1.5, 95% CI 1.1-1.9, p=0.000], insulin resistance [(r)=-1.2, 95% CI -0.8 to -1.6, p=0.000], physical activity [(r)=0.6, 95% CI 0.2-0.9, p=0.002] and monounsaturated fat intake [(r)=0.5, 95% CI 0.38-1.0, p=0.047]. CONCLUSIONS: The adiponectin level was modulated by the interaction between BMI and -11391G/A SNP; this suggests that the lifestyle rather than genetic factors modulates serum adiponectin.