Zoledronic acid conjugated calcium phosphate nanoparticles for applications in cancer immunotherapy

Zoledmnic acid (Zol) is a potent bisphosphonate drug used in cancer immunotherapy due to its ability to activate gamma delta T cells and bring about depletion of tumor-associated macrophages. Zoledronic acid pulsed monocytes are utilized for the activation and proliferation of gamma delta T cells. For adoptive gamma delta T cell transfer, isolated peripheral blood mononuclear cells (PBMC) are treated with Zol under in vitro conditions for gamma delta T cell expansion. Herein, we optimized, zoledmnate conjugated calcium phosphate nanoparticles (Zol-nCP) to improve in vitro gamma delta T cell proliferation. PBMC treated with Zol-nCP conjugates resulted in 28.7% enhancement in gamma delta T 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.