An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy

  • Nat Commun. 2016 Nov 7;7:13443. doi: 10.1038/ncomms13443.
Yichao Chen  1  2  3 ,  Rui Xia  4 ,  Yixian Huang  1  2  3 ,  Wenchen Zhao  2 ,  Jiang Li  1  2  3 ,  Xiaolan Zhang  1  2  3 ,  Pengcheng Wang  1  2 ,  Raman Venkataramanan  2 ,  Jie Fan  5 ,  Wen Xie  1  2 ,  Xiaochao Ma  1  2 ,  Binfeng Lu  3  4 ,  Song Li  1  2  3
Affiliations
  • 1. Center for Pharmacogenetics, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
  • 2. Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
  • 3. University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
  • 4. Department of Immunology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
  • 5. Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
PMID: 27819653 DOI: 10.1038/ncomms13443
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.

Products