Tumour sensitization via the extended intratumoural release of a STING agonist and camptothecin from a self-assembled hydrogel

Feihu Wang, Hao Su, Dongqing Xu, Wenbing Dai, Weijie Zhang, Zongyuan Wang, Caleb F. Anderson, Mengzhen Zheng, Richard Oh, Fengyi Wan, Honggang Cui

Research output: Contribution to journalArticlepeer-review

Abstract

Tumours with an immunosuppressive microenvironment respond poorly to therapy. Activation of the stimulator of interferon genes (STING) pathway can enhance intratumoural immune activation, but STING agonists are associated with high toxicity and degrade prematurely, which limits their effectiveness. Here, we show that the extended intratumoural release of the STING agonist cyclic di-AMP transforms the tumour microenvironment from immunosuppressive to immunostimulatory, increasing the efficacy of antitumour therapies. The STING agonist was electrostatically complexed with nanotubes comprising a peptide–drug conjugate (a peptide that binds to the protein neuropilin-1, which is highly expressed in tumours, and the chemotherapeutic agent camptothecin) that self-assemble in situ into a supramolecular hydrogel. In multiple mouse models of murine tumours, a single low dose of the STING agonist led to tumour regression and increased animal survival, and to long-term immunological memory and systemic immune surveillance, which protected the mice against tumour recurrence and the formation of metastases. Locally delivered STING agonists could help to reduce tumour immunosuppression and enhance the efficacy of a wide range of cancer therapies.

Original languageEnglish (US)
Pages (from-to)1090-1101
Number of pages12
JournalNature biomedical engineering
Volume4
Issue number11
DOIs
StatePublished - Nov 1 2020

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Computer Science Applications

Fingerprint Dive into the research topics of 'Tumour sensitization via the extended intratumoural release of a STING agonist and camptothecin from a self-assembled hydrogel'. Together they form a unique fingerprint.

Cite this