Antifouling Cyclic Peptide Nanotubes Combined with Rh–Ti₃C₂T_X Multifunctional Nanozyme for the Sensitive Detection of CA125 in Complex Biological Samples

Although linear peptides exhibit advantageous physicochemical properties and biocompatibility for antifouling biosensing applications, the intrinsic structural flexibility of natural linear peptides makes them susceptible to enzymatic degradation, compromising their long-term practical applications. To address these limitations, cyclic peptide nanotubes (CPNTs) were prepared via a self-assembly strategy of cyclic peptides, which imparted exceptional enzymatic stability due to their intramolecular hydrogen bonds and rigid tubular structure. Moreover, the densely arranged hydrophilic residues on the surface of the nanotubes (such as serine, histidine, and glutamic acid) formed a dynamic hydration layer through hydrogen bonding with free water molecules, thereby achieving a 2.7-fold enhancement in antifouling performance compared to that of linear peptides (L-pep). Concurrently, sensing interface MXene-supported ruthenium nanoparticles (Rh-Ti₃C₂T_X) exhibited dual activities simultaneously to induce a one-step cascade reaction in the presence of glucose, surpassing traditional multistep processes in catalytic efficiency. By integrating the superior antifouling properties of CPNTs with self-supplied H₂O₂ cascade catalytic signal amplification of Rh-Ti₃C₂T_X nanozyme, the constructed antifouling aptasensor achieved sensitive and accurate detection of cancer antigen 125 (CA125) in human serum, with a low detection limit of 0.005 U·mL^-1. This work not only provides insights into the development of antifouling materials but also demonstrates clinical potential for ovarian cancer marker detection in human serum.