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Combination treatment of thymoquinone-loaded gold nanoparticles and cisplatin potentiates anti-tumor activity and immunomodulatory effects in breast cancer model

Soha Gomaa; Ahlam Aboshafey; Asmaa Aladawy.

Abstract
Gold nanoparticles (AuNPs) can be used as nanocarriers for cancer chemotherapy to minimize its toxicity and increase its therapeutic efficacy. Herbal anti-tumor agent Thymoquinone (TQ) upon loading onto nanoparticles (NPs) might augment its aggregation in cancer. The goal of this study was to investigate in vivo the anti-cancer effectiveness and improvement effect of cancer chemotherapy-induced liver histological alternations of TQ–conjugated AuNPs (AuNPs/TQ composite) in combination with systemic chemotherapeutic drugs cisplatin (Cis) in tumor-bearing mice. Tumor-bearing mice were once-daily orally administered: AuNPs (21.4 µg/mouse), AuNPs/TQ conjugate (1 mg/mouse), AuNPs/TQ (1mg/mouse) + Cis (10 µg/mouse) (AuNPs/TQ + Cis10) or AuNPs/TQ (1mg/mouse) + Cis (40 µg/mouse) (AuNPs/TQ + Cis40) for 6 days. 11 days post tumor inoculations, the total numbers of tumor cells and splenocytes, flowcytometric analysis of splenic myeloid and lymphocytes surface markers as well as liver histopathological alterations were examined. Treatment mice with AuNPs/TQ + Cis40 enhanced anti-tumor activity and therapeutic efficiency of this regimen with low toxicity on healthy cells. Treatment mice with AuNPs/TQ + Cis40 resulted in expression of myeloid and helper T-cells (CD4+ T cells). Treatment of mice with free AuNPs or AuNPs/TQ conjugate showed liver histological alterations that were ameliorated by AuNPs/ TQ+ Cis40 treatment To conclude, AuNPs/TQ + Cis40 regimen has a great potential to increase anti-tumor effect, overcome resistance to chemotherapeutics and reduce side effects. This approach may offer a promising regimen for cancer therapy and more studies are required to connect the biomedical application of this regimen to diagnostic and therapeutic and approaches.

Key words: Gold nanoparticles;Thymoquinone;Cisplatin;Anti-cancer efficacy;Hepatotoxicity



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