The potential anticancer activity of different
silver nanoformulations is increasingly recognized. In the present work, we use the model of 4T1
tumor in BALB/ccmdb immunocompetent mice to analyze the impact of
citrate- and PEG-coated
silver nanoparticles (AgNPs) on the development and metastatic potential of
breast cancer. One group of mice was intragastrically administered with 1 mg/kg
body weight (b.w.) of AgNPs daily from day 1 to day 14 after
cancer cells implantation (total dose 14 mg/kg b.w.). The second group was intravenously administered twice with 1 or 5 mg/kg b.w. of AgNPs. A tendency for lowering
tumor volume on day 21 (mean volumes 491.31, 428.88, and 386.83 mm3 for control, AgNPs-PEG, and AgNPs-
citrate, respectively) and day 26 (mean volumes 903.20, 764.27, and 672.62 mm3 for control, AgNPs-PEG, and AgNPs-
citrate, respectively) has been observed in mice treated intragastrically, but the effect did not reach the level of statistical significance. Interestingly, in mice treated intragastrically with
citrate-coated AgNPs, the number of lung
metastases was significantly lower, as compared to control mice (the mean number of
metastases 18.89, 14.90, and 8.03 for control, AgNPs-PEG, and AgNPs-
citrate, respectively). No effect of AgNPs treatment on the number of lung
metastases was observed after
intravenous administration (the mean number of
metastases 12.44, 9.86, 12.88, 11.05, and 10.5 for control, AgNPs-PEG 1 mg/kg, AgNPs-PEG 5 mg/kg, AgNPs-
citrate 1 mg/kg, and AgNPs-
citrate 5 mg/kg, respectively). Surprisingly, inhibition of
metastasis was not accompanied by changes in the expression of genes associated with epithelial-mesenchymal transition. Instead, changes in the expression of
inflammation-related genes were observed. The presented results support the antitumor activity of AgNPs in vivo, but the effect was limited to the inhibition of
metastasis. Moreover, our results clearly point to the importance of AgNPs coating and route of administration for its anticancer activity. Finally, our study supports the previous findings that antitumor AgNPs activity may depend on the activation of the immune system and not on the direct action of AgNPs on
cancer cells.