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A double-edged sword effect of silver nanoparticles on angiogenesis in 4T1 breast cancer-bearing mice
Hemen Moradi-Sardareh1, Fataneh Esmaeili2, Sara Momtahan3
1Biomed Company, Oslo, Norway.
Background:
Silver nanoparticles (AgNPs) are increasingly known to have anticancer effects, but few studies have examined their adverse effects, so the underlying mechanisms are not yet fully understood. The current study investigated the critical influence of AgNPs on angiogenesis in 4T1 breast cancer-bearing mice.
Methods:
The sub-lethal dose of AgNPs (0.25 mg/kg) was carried out. Female BALB/c mice (N = 35) were divided into 7 groups; normal control, cancer control, AgNPs control (one dose of (0.25 mg/kg) AgNPs), single dose AgNPs before cancer, single dose AgNPs after cancer, 5 doses AgNPs after cancer, and doxorubicin. 4T1 breast cancer cell induction was performed subcutaneously on the left flank. Intraperitoneal (IP) administration of AgNPs and doxorubicin was carried out for all studied groups.
Results:
Weight gain was normal in all study groups except the doxorubicin-treated group. Administering AgNPs before cancer induction promotes tumorigenesis, raises MMP-2 and MMP-9 activity, and increases CD31 and Ki67 expression. The cancer control group experienced the same outcomes. On the other hand, depending on the administered doses, the injection of AgNPs after tumor induction resulted in a notable decrease in tumor volume. In the doxorubicin-treated group, similar results were observed, while a dose of AgNPs before cancer induction lead to increasing tumor volume compared to the cancer control group. The differences of biochemical markers including LDH, ALP, AST, ALT, BUN, and Cr between different groups were not significant. Significant differences were seen among all studied groups except doxorubicin and single dose AgNPs before cancer groups for serum TAC levels.
Conclusions:
It appears that AgNPs are considered a double-edged sword in the fight against cancer. AgNPs not only have anti-cancer effects on tumor size and angiogenesis, but they also might have cancer-stimulating roles. To confirm this conclusion, more detailed investigations are needed.
Insights
Silver nanoparticles (AgNPs) show a dual role in cancer, potentially inhibiting tumor growth when administered after cancer induction but promoting it when given beforehand. Further research is needed to clarify these complex effects on angiogenesis.
Area of Science:
- Nanomedicine
- Oncology
- Biochemistry
Background:
- Silver nanoparticles (AgNPs) exhibit known anticancer properties, yet their adverse effects and underlying mechanisms, particularly concerning angiogenesis, remain under-investigated.
- This study addresses the critical influence of AgNPs on angiogenesis in a 4T1 breast cancer mouse model.
Purpose of the Study:
- To investigate the dual role of silver nanoparticles (AgNPs) in breast cancer progression and angiogenesis.
- To evaluate the impact of AgNPs administration timing and dosage on tumor growth and related biomarkers.
Main Methods:
- Sub-lethal dose (0.25 mg/kg) of AgNPs administered intraperitoneally to 35 female BALB/c mice divided into 7 groups.
- Groups included normal control, cancer control, AgNPs control, AgNPs before cancer, AgNPs after cancer (single and 5 doses), and doxorubicin treatment.
- 4T1 breast cancer cells were induced subcutaneously; tumor volume, MMP-2/9 activity, and CD31/Ki67 expression were assessed.
Main Results:
- AgNPs administered before tumor induction promoted tumorigenesis, increasing MMP-2/9, CD31, and Ki67 expression, similar to the cancer control group.
- AgNPs administered after tumor induction significantly decreased tumor volume in a dose-dependent manner, comparable to doxorubicin treatment.
- No significant differences were observed in most biochemical markers (LDH, ALP, AST, ALT, BUN, Cr); serum TAC levels showed significant differences among groups, except for doxorubicin and single-dose AgNPs before cancer groups.
Conclusions:
- Silver nanoparticles (AgNPs) demonstrate a "double-edged sword" effect in cancer therapy, exhibiting both anti-cancer and potentially cancer-stimulating properties.
- The timing of AgNP administration is critical, influencing tumor growth and angiogenesis.
- Further comprehensive investigations are required to elucidate the complex mechanisms and confirm the therapeutic potential or risks of AgNPs in oncology.
