Electric Pulse Responsive Magnetic Nanoclusters Loaded with Indoleamine 2,3-Dioxygenase Inhibitor for Synergistic Immuno-Ablation Cancer Therapy

Bo Yu, Wentao Zhang, Kijung Kwak, Hyunjun Choi, Dong Hyun Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

An overlay of local ablation and immunotherapies could be one of the promising approaches to treat solid tumors, but finding the synergistic combination is still challenging with immune tolerance. Herein, electric pulse responsive iron-oxide-nanocube clusters (IONCs) loaded with indoleamine 2,3-dioxygenase inhibitors (IDOi) are prepared for the enhancement of irreversible electroporation (IRE) cell killing and modulation of the tumor immunosuppressive microenvironment (TIM). IDOi-loaded-IONCs (IDOi-IONCs) show highly responsive movement upon the application of IRE electric pulses inducing local magnetic fields. In vitro and in vivo IRE cell-killing efficiency are significantly enhanced by the IDOi-IONCs. The IRE with IDOi-IONCs also triggers IDOi release from IONCs for TIM modulation. The enhanced cell death and local IDOi release of the IRE with IDOi-IONCs demonstrate a synergistic anticancer effect in vivo with overturning the TIM. The increased infiltration of CD8+ T cells and the elevated ratio of CD8+ T cells to regulatory T cells are confirmed after the IRE with IDOi-IONCs. Further, synergistic interaction between IRE and IDOi-modulated TIM resulted in enhanced elimination of primary and secondary tumors. This proof-of-concept work illustrates a robust modality to guide immune-modulating nanoparticle-mediated immuno-ablation cancer therapies that can be easily tailored to improve its therapeutic outcome.

Original languageEnglish (US)
Pages (from-to)54415-54425
Number of pages11
JournalACS Applied Materials and Interfaces
Volume12
Issue number49
DOIs
StatePublished - Dec 9 2020

Keywords

  • immunotherapy
  • indoleamine 2,3-dioxygenase inhibitor
  • irreversible electroporation
  • local ablation
  • magnetic nanoparticles

ASJC Scopus subject areas

  • Materials Science(all)

Fingerprint

Dive into the research topics of 'Electric Pulse Responsive Magnetic Nanoclusters Loaded with Indoleamine 2,3-Dioxygenase Inhibitor for Synergistic Immuno-Ablation Cancer Therapy'. Together they form a unique fingerprint.

Cite this