Silver Nanoparticles Inhibit Metastasis of 4T1 Tumor in Mice after Intragastric but Not Intravenous Administration

Abstract

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.

The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future?

“…Migration and invasion are significant characteristics of the development and worsening of cancer [ 61 , 197 , 198 , 199 ]. Although it has been discovered that AgNPs suppress tumor invasion [ 200 ], the underlying mechanism remains unknown. It is speculated that AgNPs may inhibit the protein production of cytokines and growth factors in cancer cells, as well as the enzymatic activity of MMPs.…”

Antitumor efficacy of silver nanoparticles reduced with β-D-glucose as neoadjuvant therapy to prevent tumor relapse in a mouse model of breast cancer

“…Our results are consistent with other studies that report in tumor-bearing mice (induced with 4T1 cell line) that AgNPs can reduce tumors to an average size of 100 mm 3 ( Swanner et al, 2019 ). However, Brzóska et al (2022) evaluated a synthesis of AgNPs reduced with citrate in mice bearing tumor from a 4T1 cell line, but no reduction in tumor volume was observed. This discrepancy in results could be attributed to factors such as size, shape, and coating that are known to alter the effect of nanoparticles ( Auría et al, 2019 ).…”

Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer

“…A detailed description of the animal model used in the study is given in the previous paper [22]. Briefly, 3-month-old female BALB/ccmdb mice were subcutaneously injected into the mammary fat pad with 1 × 10 5 4T1 cells suspended in 100 µL of PBS.…”

“…Zeta potential was equal to −43 mV. PEG-coated AgNPs were obtained from citrate-coated AgNPs as described previously [22]. AgNPs were diluted in sterile water and administered to animals at a dose of 1 mg/kg.…”

“…Our recent study involved an investigation of how AgNPs, in terms of their coating and administration route, affect the development and metastatic potential of 4T1 breast cancer in BALB/ccmdb immunocompetent mice. It was found that even though AgNPs administration did not affect tumor growth kinetics, it significantly inhibited metastasis formation [22]. The effect was evidently reliant on both the coating of nanoparticles and the administration route since it was observed only after intragastric administration of citratecoated but not PEG-coated AgNPs.…”