Dual fluorescence imaging-guided programmed delivery of doxorubicin and CpG nanoparticles to modulate tumor microenvironment for effective chemo-immunotherapy

Abstract

Chemo-immunotherapy has gained increasing attention as one of most promising combination therapy strategies to battle against malignant cancer. In order to achieve a more effective synergistic chemo-immunotherapy and explain the process and mechanism of action, it is an attractive idea to merge chemo-immunotherapy with imaging-guidance and biomaterials assistance. Herein, we designed a dual fluorescence imaging-guided programmed delivery system including doxorubicin and CpG nanoparticles to modulate tumor microenvironment for effective chemo-immunotherapy. CpG self-crosslinking nanoparticles from a hydrogel ensured the long-lasting immune stimulating effect compared to the direct delivery of doxorubicin from the hydrogel. Chemotherapy drug and immunoadjuvant were co-delivery with spatio-temporal release. The immune cells from tumor microenvironment were further analyzed to reveal the possible mechanism of chemo-immunotherapy including cytotoxic CD8⁺ T lymphocytes, myeloid-derived suppressor cells and M2-like tumor-associated macrophages. Based on the co-stimulation of doxorubicin and CpG nanoparticles, the tumor microenvironment was positively regulated toward tumor-suppressive condition to generate stronger immune response for efficient chemo-immunotherapy. Moreover, dual fluorescence imaging-guided programmed delivery was tracked by own fluorescence of doxorubicin and genipin crosslinking CpG nanoparticles, respectively. Fluorescence imaging-guided programmed delivery of doxorubicin and CpG nanoparticles revealed the dynamic process of chemo-immunotherapy, providing a promising strategy for premise cancer therapy.

Keywords: Chemo-immunotherapy; CpG nanoparticles; Fluorescence imaging; Programmed delivery; Tumor microenvironment.