Near-Infrared Phototheranostic Iron Pyrite Nanocrystals Simultaneously Induce Dual Cell Death Pathways via Enhanced Fenton Reactions in Triple-Negative Breast Cancer

被引:18
作者
Zhao, Chunhua [1 ]
Liu, Zekun [1 ]
Chang, Chia-Che [2 ]
Chen, Yi-Chia [2 ]
Zhang, Qize [3 ]
Zhang, Xiao-Dong [4 ,5 ]
Andreou, Chrysalis [3 ,6 ]
Pang, Jiadong [1 ]
Liu, Ze-Xian [1 ]
Wang, Di-Yan [2 ]
Kircher, Moritz F.
Yang, Jiang [1 ,3 ]
机构
[1] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China,Canc Ctr, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, Peoples R China
[2] Tunghai Univ, Dept Chem, Taichung 40704, Taiwan
[3] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA
[4] Tianjin Univ, Dept Phys, Tianjin 300354, Peoples R China
[5] Tianjin Univ, Sch Sci, Tianjin Key Lab Low Dimens Mat Phys & Preparing Te, Tianjin 300354, Peoples R China
[6] Univ Cyprus, Dept Elect & Comp Engn, Nicosia 1678, Cyprus
基金
中国国家自然科学基金;
关键词
FeS2; nanocrystals; ferroptosis; hyperbranched PEGs; multispectral optoacoustic tomography; photothermal therapy; triple-negative breast cancer; breast cancer metastasis; PHOTOTHERMAL CONVERSION EFFICIENCY; SEMICONDUCTING POLYMER; NANOPARTICLES; RESISTANCE; INHIBITOR; THERAPY;
D O I
10.1021/acsnano.2c06629
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:4261 / 4278
页数:18
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