# Development of uMUC-1 Targeted NEMO Particles with pH-Activatable MRI Signals for Enhanced Detection of Malignant Breast Cancer Cells

## TL;DR

A new MRI contrast agent called EPPT-NEMO was developed to better detect malignant breast cancer cells by targeting them specifically and producing brighter signals than benign cells.

## Contribution

The novel contribution is the development of pH-sensitive, receptor-targeted NEMO particles that enhance MRI contrast specifically in malignant breast cancer cells.

## Key findings

- EPPT-NEMO particles produced ∼276% signal enhancement in T47D breast cancer cells compared to ∼57% in benign MCF10A cells.
- The particles localized to endosomes and lysosomes, confirming pH-activatable signal generation.
- The contrast agent showed potential to improve breast cancer diagnosis accuracy within clinically relevant timeframes.

## Abstract

Magnetic resonance
imaging (MRI) detects more breast cancers than
mammography due to its superior soft tissue contrast; however, it
still misdiagnoses 40% of benign tumors as malignant due to clinically
used nonspecific contrast agents (e.g., gadolinium chelates). To overcome
this limitation, we developed receptor-targeted, pH-sensitive Nano-Encapsulated
Manganese Oxide (NEMO) particles as an alternative T1-weighted MRI contrast agent. A breast cancer targeting
peptide, EPPT, against underglycosylated mucin-1, promotes preferential
endocytosis of NEMO particles by malignant cells and specific activation
of the MRI signal inside low pH endosomes/lysosomes. In just 30 min,
EPPT-NEMO particles produced rapid and robust T1-weighted MRI contrast inside T47D breast cancer cells that
reached ∼276% signal enhancement, which was significantly brighter
than MCF10A benign control cells (∼57% enhancement). Mn cellular
content further confirmed peptide targeting specificity, while confocal
microscopy showed the colocalization of EPPT-NEMO particles with endosomes
and lysosomes. EPPT-NEMO particles show promise as alternative T1-weighted MRI contrast agents, producing significantly
brighter signals in breast cancer cells compared to benign cells within
clinically relevant timeframes. These advancements in targeted MRI
contrast agents could lead to improved accuracy in breast cancer diagnosis
and ultimately to better patient outcomes.