Selective Isolation and Colorimetric Detection of Her2-Overexpressing Breast Cancer-Derived Exosomes in Mouse Urine Using Magnetic Nanoparticle Complex Polydiacetylene Nanoparticles

Breast cancer (BC) is one of the major health problems worldwide. Approximately 20–25% of BC patients overexpress human epidermal growth factor receptor 2 (HER2), a marker for aggressive BC. Early HER2-overexpression detection greatly increases patient survival; however, appropriate diagnostics and therapeutics are not yet equally available in all countries. We have developed an equipment-free, low-cost, and easy-to-use polydiacetylene (PDA)-based colorimetric sensor for HER2-overexpressing BC detection, designed for use in low- and middle-income countries (LMICs). PDA nanoparticles were first prepared through thin-film hydration. Subsequently, hydrophilic magnetic nanoparticles and HER2 antibodies were sequentially conjugated to them. The synthesized HER2-MPDA can be concentrated and separated by a magnetic field while inheriting the optical characteristics of PDA. The specific binding of the HER2 antibody of HER2-MPDA to the HER2 receptor in HER2-overexpressing exosomes induces a rearrangement of the molecular structure within the PDA backbone, altering its electronic properties and inducing a color change blue to red in HER2-MPDA. This colorimetric sensor, whose color changes upon binding to HER2-overexpressing exosomes, can be separated with a magnet immediately after the reaction. Finally, the performance of HER2-MPDA was evaluated in detecting HER2-overexpressing exosomes in the culture medium of HER2-overexpressing BC cells and mouse urine samples from a HER2-overexpressing BC mouse model. We hope that this sensor can be an effective point-of-care platform to reduce mortality due to HER2-overexpressing BC in LMICs.