Zoledronic acid conjugated calcium phosphate nanoparticles for applications in cancer immunotherapy

Abstract

Zoledronic acid (Zol) is a potent bisphosphonate drug used in cancer immunotherapy due to its ability to activate γδT cells and bring about depletion of tumor-associated macrophages. Zoledronic acid pulsed monocytes are utilized for the activation and proliferation of γδT cells. For adoptive γδT cell transfer, isolated peripheral blood mononuclear cells (PBMC) are treated with Zol under in vitro conditions for γδT cell expansion. Herein, we optimized, zoledronate conjugated calcium phosphate nanoparticles (Zol-nCP) to improve in vitro γδT cell proliferation. PBMC treated with Zol-nCP conjugates resulted in 28.7% enhancement in γδT cell proliferation in comparison to free Zol. In addition, the treatment of RAW 264.7 macrophages with Zol-nCP resulted in 25% enhanced Zol mediated toxicity compared to the bare drug. This enhancement in toxicity to macrophages can be utilized for better depletion of tumor-associated macrophages compared to free Zol. The development of this nanoconjugate may have great potential in enhancing the clinical efficacy of bisphosphonate-mediated cancer immunotherapy.