Near-infrared phototheranostic iron pyrite nanocrystals simultaneously induce dual cell death pathways via enhanced fenton reactions in triple-negative breast cancer Journal Article


Authors: Zhao, C.; Liu, Z.; Chang, C. C.; Chen, Y. C.; Zhang, Q.; Zhang, X. D.; Andreou, C.; Pang, J.; Liu, Z. X.; Wang, D. Y.; Kircher, M. F.; Yang, J.
Article Title: Near-infrared phototheranostic iron pyrite nanocrystals simultaneously induce dual cell death pathways via enhanced fenton reactions in triple-negative breast cancer
Abstract: Triple-negative breast cancer (TNBC) is considered more aggressive with a poorer prognosis than other breast cancer subtypes. Through systemic bioinformatic analyses, we established the ferroptosis potential index (FPI) based on the expression profile of ferroptosis regulatory genes and found that TNBC has a higher FPI than non-TNBC in human BC cell lines and tumor tissues. To exploit this finding for potential patient stratification, we developed biologically amenable phototheranostic iron pyrite FeS2 nanocrystals (NCs) that efficiently harness near-infrared (NIR) light, as in photovoltaics, for multispectral optoacoustic tomography (MSOT) and photothermal ablation with a high photothermal conversion efficiency (PCE) of 63.1%. Upon NIR irradiation that thermodynamically enhances Fenton reactions, dual death pathways of apoptosis and ferroptosis are simultaneously triggered in TNBC cells, comprehensively limiting primary and metastatic TNBC by regulating p53, FoxO, and HIF-1 signaling pathways and attenuating a series of metabolic processes, including glutathione and amino acids. As a unitary phototheranostic agent with a safe toxicological profile, the nanocrystal represents an effective way to circumvent the lack of therapeutic targets and the propensity of multisite metastatic progression in TNBC in a streamlined workflow of cancer management with an integrated image-guided intervention. © 2023 American Chemical Society.
Keywords: genetics; cell death; breast cancer; cell line, tumor; cell culture; tomography; diagnosis; tumor cell line; iron; nanoparticles; nanoparticle; diseases; multi-spectral; cell signaling; triple negative breast cancer; triple-negative breast cancer; infrared devices; nanocrystals; photothermal therapy; cancer metastasis; ferroptosis; humans; human; pyrites; breast cancer metastasis; triple-negative breast cancers; triple negative breast neoplasms; multispectral optoacoustic tomography; optoacoustic tomography; conversion efficiency; pyrite; fes2nanocrystal; hyperbranched; hyperbranched peg; fes<sub>2</sub> nanocrystals; hyperbranched pegs
Journal Title: ACS Nano
Volume: 17
Issue: 5
ISSN: 1936-0851
Publisher: American Chemical Society  
Date Published: 2023-03-14
Start Page: 4261
End Page: 4278
Language: English
DOI: 10.1021/acsnano.2c06629
PUBMED: 36706095
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Moritz Florian Kircher
    55 Kircher
  2. Chrysafis   Andreou
    22 Andreou
  3. Jiang Yang
    7 Yang
  4. Qize Zhang
    9 Zhang