Synthetic Immunogenic Cell Death Mediated by Intracellular Delivery of STING Agonist Nanoshells Enhances Anticancer Chemo-immunotherapy

Saborni Chattopadhyay, Yu Han Liu, Zih Syun Fang, Chi Long Lin, Jung Chen Lin, Bing Yu Yao, Che Ming Jack Hu

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Many favorable anticancer treatments owe their success to the induction immunogenic cell death (ICD) in cancer cells, which results in the release of endogenous danger signals along with tumor antigens for effective priming of anticancer immunity. We describe a strategy to artificially induce ICD by delivering the agonist of stimulator of interferon genes (STING) into tumor cells using hollow polymeric nanoshells. Following intracellular delivery of exogenous adjuvant, subsequent cytotoxic treatment creates immunogenic cellular debris that spatiotemporally coordinate tumor antigens and STING agonist in a process herein termed synthetic immunogenic cell death (sICD). sICD is indiscriminate to the type of chemotherapeutics and enables colocalization of exogenously administered immunologic adjuvants and tumor antigens for enhanced antigen presentation and anticancer adaptive response. In three mouse tumor models, sICD enhances therapeutic efficacy and restrains tumor progression. The study highlights the benefit of delivering STING agonists to cancer cells, paving ways to new chemo-immunotherapeutic designs.

Original languageEnglish
Pages (from-to)2246-2256
Number of pages11
JournalNano letters
Volume20
Issue number4
DOIs
Publication statusPublished - 2020 Apr 8

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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