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An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy

Author

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  • Yichao Chen

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh
    University of Pittsburgh Cancer Institute, University of Pittsburgh)

  • Rui Xia

    (School of Medicine, University of Pittsburgh)

  • Yixian Huang

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh
    University of Pittsburgh Cancer Institute, University of Pittsburgh)

  • Wenchen Zhao

    (School of Pharmacy, University of Pittsburgh)

  • Jiang Li

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh
    University of Pittsburgh Cancer Institute, University of Pittsburgh)

  • Xiaolan Zhang

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh
    University of Pittsburgh Cancer Institute, University of Pittsburgh)

  • Pengcheng Wang

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh)

  • Raman Venkataramanan

    (School of Pharmacy, University of Pittsburgh)

  • Jie Fan

    (School of Medicine, University of Pittsburgh)

  • Wen Xie

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh)

  • Xiaochao Ma

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh)

  • Binfeng Lu

    (University of Pittsburgh Cancer Institute, University of Pittsburgh
    School of Medicine, University of Pittsburgh)

  • Song Li

    (Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
    School of Pharmacy, University of Pittsburgh
    University of Pittsburgh Cancer Institute, University of Pittsburgh)

Abstract

Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG2k-Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG2k-Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast cancer and melanoma mouse models.

Suggested Citation

  • Yichao Chen & Rui Xia & Yixian Huang & Wenchen Zhao & Jiang Li & Xiaolan Zhang & Pengcheng Wang & Raman Venkataramanan & Jie Fan & Wen Xie & Xiaochao Ma & Binfeng Lu & Song Li, 2016. "An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13443
    DOI: 10.1038/ncomms13443
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    Cited by:

    1. Zhangyi Luo & Yixian Huang & Neelu Batra & Yuang Chen & Haozhe Huang & Yifei Wang & Ziqian Zhang & Shichen Li & Chien-Yu Chen & Zehua Wang & Jingjing Sun & Qiming Jane Wang & Da Yang & Binfeng Lu & Ja, 2024. "Inhibition of iRhom1 by CD44-targeting nanocarrier for improved cancer immunochemotherapy," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Zhiren Wang & Wenpan Li & Yanhao Jiang & Tuyen Ba Tran & Leyla Estrella Cordova & Jinha Chung & Minhyeok Kim & Georg Wondrak & Jennifer Erdrich & Jianqin Lu, 2023. "Sphingomyelin-derived nanovesicles for the delivery of the IDO1 inhibitor epacadostat enhance metastatic and post-surgical melanoma immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Ziyang Cao & Dongdong Li & Liang Zhao & Mengting Liu & Pengyue Ma & Yingli Luo & Xianzhu Yang, 2022. "Bioorthogonal in situ assembly of nanomedicines as drug depots for extracellular drug delivery," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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