An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy

Yichao Chen, Rui Xia, Yixian Huang, Wenchen Zhao, Jiang Li, Xiaolan Zhang, Pengcheng Wang, Raman Venkataramanan, Jie Fan, Wen Xie, Xiaochao Ma, Binfeng Lu and Song Li ()
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Yichao Chen: Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
Rui Xia: School of Medicine, University of Pittsburgh
Yixian Huang: Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
Wenchen Zhao: School of Pharmacy, University of Pittsburgh
Jiang Li: Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
Xiaolan Zhang: Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
Pengcheng Wang: Center for Pharmacogenetics, 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
Xiaochao Ma: Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh
Binfeng Lu: University of Pittsburgh Cancer Institute, University of Pittsburgh
Song Li: Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13443

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