2. Academic Validation
  3. An immunostimulatory dual-functional nanocarrier that improves cancer immunochemotherapy

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

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.

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