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Tumor and dendritic cell dual-targeting nanocarriers maximize the therapeutic potential of IDO1 inhibitor in vivo

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Abstract

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.

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Acknowledgements

The authors acknowledge the support from the National Natural Science Foundation of China (Nos. 81773648 and 81973267) and the Zhejiang Provincial Natural Science Foundation of China (Nos. LD19H300001 and LQ20H300004).

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Authors and Affiliations

  1. Ocean College, Zhejiang University, Zhoushan, 316021, China

    Tong Yu, Hong Yuan & Fuqiang Hu

  2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    Tong Yu, Xiangyu Jin, Fangying Yu, Xiqin Yang, Yingping Zeng, Tingting Meng, Hong Yuan & Fuqiang Hu

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  1. Tong Yu
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  3. Fangying Yu
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Correspondence to Fuqiang Hu.

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Yu, T., Jin, X., Yu, F. et al. Tumor and dendritic cell dual-targeting nanocarriers maximize the therapeutic potential of IDO1 inhibitor in vivo. Nano Res. 15, 9204–9214 (2022). https://doi.org/10.1007/s12274-022-4597-7

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  • DOI: https://doi.org/10.1007/s12274-022-4597-7

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