Hormone-Coated NanoContrast Agent Promotes ER+ Breast Cancer Cells 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 the mortality rates by 20%. High specificity and sensitivity is thus a constant request in breast cancer screening. In cases where breast tumors cannot be identified, such as the case 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 fast, 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, 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 act dually as fluorescence and M/CT contrast probes, amplifying the signal at the targeting site due to affinity-empowered NP localization within cells. Material preparation, small molecules 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 to our knowledge study reporting hormone-coated NPs as a new M/CT contrast agent for breast cancer screening.