Hormone-coated nanocontrast agent promotes ER+ breast cancer cell detection

Abstract

Breast cancer along with colorectal and lung cancer contribute to ∼51% of all female cancers and significantly affect women's health. Breast cancer screening with standard medical imaging techniques such as ultrasound, MRI, digital mammography (M; low-energy X-rays), contrast-enhanced mammography (CEM), and X-ray computed tomography (CT; high-energy X-rays) can reduce mortality rates by 20%. High specificity and sensitivity are thus crucial in breast cancer screening. In cases where breast cancer cannot be identified, such as cases of dense breast tumors, CEM is used. However, all the FDA-approved M/CT contrast probes are non-specific blood pool agents that target tumors passively, clear quickly, require high doses, and can lead to side effects. Engineering ligand-specific nanoparticles (NPs) as molecular imaging diagnostic probes that can selectively recognize hormone receptors of breast cancer cells, which account for 70–80% of breast cancer cases, and internalize them, could allow for early identification of tumors/micro-tumors at low metal amounts, lower the imaging sensitivity detection limits, and reduce side effects related to non-specificity (non-targeted probes). Herein, we report on estrogen receptor (ER)-targeting NPs of ∼4 nm that can selectively bind and internalize to ER+ breast cancer cells, and dually as fluorescence or M/CT contrast probes, amplifying the signal at the targeting site due to affinity-empowered NP localization within cells. NP preparation, small molecule synthesis, bioconjugation, material characterization, NP/cell internalization and binding studies, as well as micro-CT analysis are described in detail and compared with controls. This is the first study to our knowledge to report hormone-coated NPs as a new M/CT contrast agent for breast cancer screening.