Doxorubicin and folic acid-loaded zinc oxide nanoparticles-based combined anti-tumor and anti-inflammatory approach for enhanced anti-cancer therapy.

BACKGROUND: Zinc oxide nanoparticles (ZnONPs) have impressively shown their efficacy in targeting and therapy of cancer. The present research was designated to investigate the potential of ZnONP nanocomposites as a cancer chemotherapeutic-based drug delivery system and to assess the anti-tumor and anti-inflammatory effectiveness of ZnONP nanocomposites combination with systemic chemotherapeutic drugs doxorubicin (DOX) and folic acid (FA) in Ehrlich ascites carcinoma (EAC) tumor cell line both in vitro and in vivo. METHODS: Anti-tumor potential of ZnONP nanocomposites: ZnONPs, ZnONPs/FA, ZnONPs/DOX and ZnONPs/DOX/FA against EAC tumor cell line was evaluated in vitro by MTT assay. Anti-tumor and anti-inflammatory efficacy of ZnONP nanocomposites were analyzed in vivo by examination of the proliferation rate and apoptosis rate of EAC tumor cells by flow cytometry, splenocytes count, level of inflammatory markers interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), as well as liver and kidney function in EAC-challenged mice. RESULTS: In vitro results showed that ZnONP nanocomposites showed a high anti-proliferative potency against EAC tumor cells. Furthermore, the in vivo study revealed that the treatment EAC-challenged mice with ZnONPs, ZnONPs/DOX, ZnONPs/FA and ZnONPs/DOX/FA hindered the proliferation rate of implanted EAC tumor cells through lowering their number and increasing their apoptosis rate. Moreover, the treatment of EAC-challenged mice with ZnONPs/DOX/FA markedly decreased the level of IL-6 and TNF-α and remarkably ameliorated the liver and kidney damages that were elevated by implantation of EAC tumor cells, restoring the liver and kidney functions to be close to the naïve mice control. CONCLUSION: ZnONP nanocomposites may be useful as a cancer chemotherapeutic-based drug delivery system. ZnONP nanocomposites: ZnONPs/DOX, ZnONPs/FA and ZnONPs/DOX/FA regimen may have anti-inflammatory approaches and a great potential to increase anti-tumor effect of conventional chemotherapy, overcoming resistance to cancer systemic chemotherapeutics and reducing their side effects, offering a promising regimen for cancer therapy.