Vinyl-functionalized covalent organic frameworks with photoelectric property and light-responsive oxidase-mimetic activity for photoelectrochemical and colorimetric dual-mode assay of PTP1B activity

Abstract

The sensitive and precise assay of protein tyrosine phosphatase 1B (PTP1B) activity plays a considerable role in clinical diagnosis and cancer therapy. Herein, a photoelectrochemical (PEC)-colorimetric (CL) dual-mode biosensor based on magnetic Fe3O4 nanospheres and vinyl-functionalized covalent organic framework (COF-V) with photoelectric property and light-responsive oxidase-mimetic activity was developed for PTP1B activity assay. Fe3O4 nanospheres modified with polydopamine (PDA) and chelated Ti4+ (Fe3O4@PDA-Ti4+) were synthesized by the self-polymerization of dopamine and the chelation reaction between hydroxyl groups in the PDA shell and Ti4+. Subsequently, the PTP1B-specific peptide (P-peptide) was modified on the surface of Fe3O4@PDA-Ti4+ nanosphere via the formation of Ti-O-P bonds between Ti4+ and phosphate group on the P-peptide. Before PTP1B activity assay, COF-V was introduced to the Fe3O4@PDA-Ti4+/P-peptide complex by thiol-ene click reaction of the vinyl group on COF-V with the thiol group of P-peptide, and the Fe3O4@PDA-Ti4+/P-peptide/COF-V complex was obtained. With addition of PTP1B, it can specifically identify and dephosphorylate the P-peptide, resulting in the release of some P-peptide and COF-V from the Fe3O4@PDA-Ti4+/P-peptide/COF-V complex. Then, the undamaged Fe3O4@PDA-Ti4+/P-peptide/COF-V complex was obtained by magnetic separation and used for PEC and CL analysis. Based on the excellent photoelectric property and light-responsive oxidase-mimetic activity of COF-V, PTP1B activity was sensitively assayed, and the linear ranges of 0.01 ng mL−1–1000 ng mL−1 (detection limit, 0.006 ng mL−1) for PEC technique and 0.1 ng mL−1–1000 ng mL−1 (detection limit, 0.03 ng mL−1) for CL method were obtained. Such a design opens a new avenue to detect protein phosphatases activity in biomedical study, disease diagnosis, and cancer treatment.