Poly(3-Hexylthiophene) Based Bioelectronic Interface Using Conducting Nanofibers (CNFs) for the Sensitive Determination of Folate Receptor Cancer Biomarkers in Human Plasma

Folate receptors (FRs) are important biomarkers that can indicate the presence of various cancers. Sensitive and accurate detection of FRs is crucial for early cancer diagnosis and treatment. The current methods of FRs detection have high cost, potential cytotoxicity, and complex production by relying on metallic nanomaterials, or have low electrical conductivity and sensitivity such as biopolymers. To address these challenges, a new approach using conducting nanofibers (CNFs) as bioelectronic surface was developed. A composite of sodium alginate (SA), a bio-friendly polymer, poly-ethylene oxide (PEO), an antifouling polymer, and poly(3-hexylthiophene) (P3HT), a semi-conducting organic polymer nanofiber was synthesized, with folic acid conjugated to the CNFs as a biorecognition element to target (FRs). The electrochemical and electrical properties were evaluated through cyclic voltammetry and electrochemical impedance spectroscopy in a solution containing both a redox marker and free redox species. The CNFs exhibit electroactivity in buffer solution without a redox marker, owing to the electronic properties of the P3HT of EIS readout. The obtained biosensor significantly improved sensitivity, enabling the detection of FRs with a limit of detection (LOD) of 0.12 pM in human plasma, the high sensitivity compared to all previous approaches and a 25-fold improvement compared to the sensor described in our previous study, with improved selectivity. Additionally, the results showed a good biocompatibility toward MCF-7 breast cancer cells, which opens the way for their use as theragnostic nanoprobes for cancer cells diagnosis and therapy. This study provided a simple, low cost and sensitive analytical approach for folate receptor detection.