Bioengineered Polymer Nanobeads for Isolation and Electrochemical Detection of Cancer Biomarkers.

Early sensitive diagnosis of cancer is critical for enhancing treatment success. We previously bioengineered multifunctional core-shell structures composed of a poly-3-hydroxybutyrate (PHB) core densely coated with protein functions for uses in bioseparation and immunodiagnostic applications. Here, we report bioengineering of Escherichia coli to self-assemble PHB inclusions that codisplay a ferritin-derived iron-binding peptide and the protein A-derived antibody-binding Z domain. The iron-binding peptide mediated surface coating with a ferrofluid imparting superparamagnetic properties, while the Z domain remained accessible for binding of cancer biomarker-specific antibodies. We demonstrated that these nanobeads can specifically bind biomarkers in complex mixtures, enabling efficient magnetic separation toward enhanced electrochemical detection of cancer biomarkers such as methylated DNA and exosomes from cancer cells. Our study revealed that superparamagnetic core-shell structures can be derived from biological self-assembly systems for uses in sensitive and specific electrochemical detection of cancer biomarkers, laying the foundation for engineering advanced nanomaterials for diverse diagnostic approaches.