IFN-γ/Doxorubicin Complex Nanoparticles for Enhancing Therapy in the Context of Human Ovarian Carcinoma

Abstract

The cytokine interferon gamma (IFN-γ) and doxorubicin mono-therapy has been approved by the Food and Drug Administration (FDA) for the treatment of tumors. The importance of IFN-γ in the immune system lies in its immunomodulatory effects, and the importance of doxorubicin in antitumor therapy lies in inhibiting RNA and DNA synthesis. In this work, the role of IFN-γ in the antitumor activity in combination with doxorubicin was investigated. Meanwhile, IFN-γ was used as a vehicle to load doxorubicin over immunotherapy and chemotherapy for synergistic therapy. IFN-γ/doxorubicin complex nanoparticles were prepared by a fusion method with a size of approximately 13 nm and a low polydispersity index. The doxorubicin release profile was analyzed with different pH ranges, and it showed an enhanced release in acidic pH. The ability of IFN-γ/doxorubicin complex nanoparticles to induce human ovarian carcinoma cell (Skov 3) apoptosis was evaluated by the cytotoxicity test. The cellular uptake of IFN-γ/doxorubicin complex nanoparticles was time-dependent, and the IFN-γ/doxorubicin complex nanoparticles showed a higher apoptosis efficiency than free doxorubicin by flow cytometry analysis and fluorescence imaging. This work bridged IFN-γ with doxorubicin to utilize their potential for antitumor activities, opening new avenues for their use in clinical settings.