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  1. Home
  3. Chirality-driven Immune Checkpoint Modulation By Chiral Iridium(iii) Nanoparticles.
  1. Home
  3. Chirality-driven Immune Checkpoint Modulation By Chiral Iridium(iii) Nanoparticles.

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Chirality-Driven Immune Checkpoint Modulation by Chiral Iridium(III) Nanoparticles.

Lu Zhu1,2,3, Ze Wen2, Maokai Yu1

  • 1School of Life Sciences, Nanjing University, Nanjing 210023, China.

Journal of the American Chemical Society
|April 22, 2026

View abstract on PubMed

Summary
This summary is machine-generated.

Chiral iridium nanoparticles precisely target PD-L1, enhancing tumor targeting and anticancer immunity. Delta configurations show superior efficacy in activating immune responses and remodeling the tumor microenvironment.

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Area of Science:

  • Nanotechnology and Materials Science
  • Immunology and Cancer Therapy
  • Medicinal Chemistry

Background:

  • Immune checkpoint inhibitors (ICIs) offer advanced cancer treatment but lack precise targeting accuracy.
  • Developing novel strategies for precise targeting is crucial to enhance ICI efficacy.
  • Chiral nanoparticles can potentially improve interactions with chiral biomolecules like immune checkpoints.

Purpose of the Study:

  • To construct metal-centered chiral iridium(III) nanoparticles (NPs) for enhanced immune checkpoint targeting.
  • To investigate the chirality-dependent biological activities and tumor targeting capabilities of these NPs.
  • To evaluate the impact of chiral NPs on anticancer immune responses and tumor microenvironment remodeling.

Main Methods:

  • Synthesis of a pair of metal-centered chiral iridium(III) nanoparticles, Δ-IrBMS8-NPs and Λ-IrBMS8-NPs, with a BMS-8 moiety.
  • Evaluation of nanoparticle compatibility with immune checkpoint biomacromolecules without nanocarriers.
  • Assessment of tumor targeting enhancement, *in vivo* anticancer immune responses, and immune cell activation.

    • Main Results:

    • Δ-IrBMS8-NPs demonstrated a 129-fold enhancement in tumor targeting via stereoselective binding to PD-L1.
    • Chiral nanoparticles exhibited distinct chirality-dependent biological activities.
    • Enhanced anticancer immune responses were observed, including cytokine pathway activation in dendritic cells and CD8+ T cell recruitment.

    Conclusions:

    • This study pioneers the use of nanoscale metal-centered chirality for precise immune checkpoint targeting.
    • Delta configurations play a pivotal role in enhancing anticancer immune responses.
    • The findings pave the way for rational design of effective metal-based immunotherapies.