Advanced materials (Deerfield Beach, Fla.)Oct 7, 2026

Using CRISPR-Enhanced Nanocatalysts to Trigger Iron-Dependent Cell Death in Triple-Negative Breast Cancer

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 8, 2026

Abstract

The nanotherapeutic achieved ≈98% tumor regression in an orthotopic model of luminal androgen receptor subtype triple-negative breast cancer.

A biomimetic nanotherapeutic was developed using single-atom iron nanocatalysts co-loaded with a CRISPR-Cas9 plasmid targeting Glutathione Peroxidase 4.
Efficient disruption of Gpx4 was observed, which may enhance the ferroptotic process.
The treatment resulted in markedly extended survival in the tested model.
Transcriptomic profiling indicated significant changes in the tumor's molecular landscape.
Activation of the DNA damage response and p53 signaling pathways was associated with increased cancer cell ferroptosis.

Simplified

The luminal androgen receptor (LAR) subtype of triple-negative breast cancer (TNBC) represents a formidable therapeutic challenge, necessitating sophisticated strategies that exploit unique tumor vulnerabilities. In the present work, we introduce a biomimetic nanotherapeutic that integrates single-atom iron nanocatalysts (FeSA) co-loaded with a CRISPR-Cas9 plasmid targeting Glutathione Peroxidase 4 (Gpx4), the key regulator of ferroptosis, and is camouflaged with a homologous cancer cell membrane to ensure precise tumor tropism and excellent biocompatibility. In an orthotopic LAR-TNBC model, the nanotherapeutic achieved ∼98% tumor regression and markedly extended survival. Comprehensive mechanistic analyses confirmed efficient on-target Gpx4 disruption, which synergistically amplified the FeSA-catalyzed ferroptotic cascade. Unbiased transcriptomic profiling further revealed extensive reprogramming of the tumor molecular landscape, resulting in significant cancer cell ferroptosis by DNA damage response and p53 signaling pathway activation. This work establishes a highly synergistic and targeted approach, presenting a potent therapeutic modality for aggressive and chemoresistant malignancies.

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Using CRISPR-Enhanced Nanocatalysts to Trigger Iron-Dependent Cell Death in Triple-Negative Breast Cancer

Abstract

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