Novel estrogen receptor ß/histone deacetylase dual-targeted near-infrared fluorescent probes as theranostic agents for imaging and treatment of prostate cancer.

Estrogen receptor (ER) ß and histone deacetylases (HDACs), when overexpressed, are associated closely with the occurrence and development of prostate cancer and are, therefore, considered important targets and biomarkers used in the clinical treatment of prostate cancer. The present study involved the design and synthesis of the first ERß and HDAC dual-target near-infrared fluorescent probe with both imaging capacity and antitumor activity for prostate cancer. Both P1 and P2 probes exhibited excellent ERß selectivity, with P1 being almost exclusively selective for ERß compared to ERα. In addition, P1 exhibited good optical properties, such as strong near-infrared emission, large Stokes shift, and better anti-interference ability, along with excellent imaging ability for living cells. P1 also exhibited potent inhibitory activity against HDAC6 and DU-145 cells, with IC50 values of 52 nM and 0.96 µM, respectively. Further, P1 was applied successfully for the in vivo imaging of prostate cancer in a mouse model, and significant in vivo antitumor efficacy was achieved. The developed dual-target NIR fluorescent probe is expected to serve as an effective tool in the research on prostate cancer, leading to novel insights for the theranostic study of diseases related to ERß and HDACs.

Anticancer or carcinogenic? The role of estrogen receptor ß in breast cancer progression.

Estrogen receptor ß (ERß) is closely related to breast cancer (BC) progression. Traditional concepts regard ERß as a tumor suppressor. As studies show the carcinogenic effect of ERß, some people have come to a new conclusion that ERß serves as a tumor suppressor in estrogen receptor α (ERα)-positive breast cancer, while it is a carcinogen in ERα-negative breast cancer. However, we re-examine the role of ERß and find this conclusion to be misleading based on the last decade's research. A large number of studies have shown that ERß plays an anticancer role in both ERα-positive and ERα-negative breast cancers, and its carcinogenicity does not depend solely on the presence of ERα. Herein, we review the anticancer and oncogenic effects of ERß on breast cancer progression in the past ten years, discuss the mechanism respectively, analyze the main reasons for the inconsistency and update ERß selective ligand library. We believe a detailed and continuously updated review will help correct the one-sided understanding of ERß, promoting ERß-targeted breast cancer therapy.

Estrogen receptor ß-targeted hypoxia-responsive near-infrared fluorescence probes for prostate cancer study.

Aberrant expression of estrogen receptor ß (ERß) and tumor hypoxia have been observed in castration-resistant prostate cancer (CRPC); therefore, hypoxia-responsive labeling of ERß will be beneficial for the early diagnosis and treatment of CRPC. Herein, we report the first ERß-targeted hypoxia-responsive near-infrared fluorescent probes, which showed superior ERß selectivity and favorable optical properties. These two probes exhibited excellent hypoxia responsiveness and specific mitochondrial ERß imaging ability in CRPC cells. In addition, P1 displayed strong anti-interference ability and good tumor imaging capacity in vivo, contributing to effective diagnosis of CRPC. Mechanistic studies, including high resolution mass spectrometry (HRMS) and density functional theory (DFT) calculations, showed that the introduction of a nitro group quenched the probe fluorescence by inducing a PET effect, while in the hypoxic tumor microenvironment, reduction of the nitro group blocked the PET effect and turned on the probe fluorescence. These novel ERß-targeted hypoxia-responsive near-infrared fluorescent probes may promote the study of prostate cancer.

Estrogen Receptor ß-Targeted Near-Infrared Inherently Fluorescent Probe: A Potent Tool for Estrogen Receptor ß Research.

Estrogen receptor ß (ERß) is associated with many diseases, and ERß probes can help to reveal the complex role of ERß and promote the development of ERß-targeted therapy. Herein, we designed and synthesized the first ERß-targeted near-infrared (NIR) inherently fluorescent probe P5, which showed the advantages of high ERß selectivity, good optical properties, and excellent ERß imaging capability in living cells. The probe was successfully utilized to explore ERß motion characteristic, and for the first time, the diffusion coefficient of ERß was obtained. Moreover, P5 was also successfully applied to the in vivo imaging of ERß in the prostate cancer mice model. Therefore, this ERß-targeted NIR probe might be employed as a potential tool for the research of ERß and related diseases.