Structure-Based Design of a Selective Class I Histone Deacetylase (HDAC) Near-Infrared (NIR) Probe for Epigenetic Regulation Detection in Triple-Negative Breast Cancer (TNBC)

Abnormally
high levels of class I histone deacetylases (HDACs)
are associated with triple-negative breast cancer (TNBC) proliferation,
malignant transformation, and poor prognosis of patients. Herein,
we report a near-infrared imaging probe for TNBC detection via visualizing
class I HDACs. Conjugating Cy5.5 to a cyclic depsipeptide inhibitor,
we obtained the probe (20-Cy5.5) that retained desirable
class I HDAC affinity and selectivity. Then, this probe could visualize
epigenetic changes by class I HDACs in TNBC MDA-MB-231 cells and in
xenograft tumor models in real time. Treatment with suberoylanilide
hydroxamic acid (SAHA) significantly reduced the uptake of the probe
in tumors, suggesting its potential use in evaluation of therapeutic
responses of HDACi-mediated therapy. Moreover, 20-Cy5.5
could detect class I HDAC expression in TNBC lung metastasis. This
novel NIR probe that achieves tumor class I HDAC imaging not only
leads to a better understanding of epigenetic regulation in tumors
but also has great potential for improving the TNBC diagnosis and
treatment.