Tumor and Dendritic Cell Dual-Targeting Nanocarriers Maximize the Therapeutic Potential of IDO1 Inhibitor in Vivo

Researches on indoleamine-2,3-dioxygenase-1 (IDO1), a neoplastic pathogenesis-related protein, have provided a new angle of view to regulate malignancy-related immunosuppression. However, the therapeutic efficacy of IDO1 inhibitors is subject to key limitations as both cancer and dendritic cells tend to be trapped in the IDO1-mediated immune dysfunction, which poses challenges to the inhibitory potency of drug regimens in multiple targets. Here, we report on the fabrication technique of a biomimetic nanocarrier that is endowed with the whole array of cancer cell membrane proteins for encapsulating the most used IDO1 probe indoximod (IND). By fully utilizing the homologous adhesion proteins and antigenic motifs on cytomembrane, these nanoparticulate particles are capable of infiltrating tumors and actively accumulating in cancer and dendritic cells, as well as hitching a ride on dendritic cells to tumor-draining lymph nodes. Ultimately, by increasing the distribution of drugs in both tumor cells and dendritic cells in tumor-draining lymph nodes, these formulations greatly enhance the efficacy of IND without the aid of chemotherapeutic drugs, achieving substantial control of tumor growth. Overall, this leverage of bionanotechnology maximizes the therapeutic potential of IND and can provide a theoretical reference for the clinical application of IDO1 inhibitors.