Enantioselective Glucose Oxidase Adsorption on Helical Polyaniline for In Vitro Antitumor Effect

Chiral nanomaterials have drawn considerable attention across biological research. However, in-depth study linking enantioselective protein adsorption on chiral nanomaterials to antitumor efficacy is still scarce. In this study, chiral helical polyaniline (PANI) with left-handedness (M-PANI) and right-handedness (P-PANI) are constructed. Thermodynamic study and molecular dynamics simulations reveal the higher binding affinity of P-PANI toward glucose oxidase (GOx) than M-PANI. As a result, a greater quantity of GOx is adsorbed onto P-PANI, leading to the chirality-dependent amount of GOx in M/P-PANI@GOx. In addition, P-PANI achieves stronger adsorption efficiency of D-glucose compared with M-PANI. Benefiting from these dual enantioselective effects, P-PANI@GOx displays superior catalytic efficiency for D-glucose oxidation. Furthermore, the M/P-PANI@GOx is found to exhibit pH-responsive photothermal performance. Upon D-glucose oxidation, the higher activity of P-PANI@GOx causes a lower pH. Consequently, it induces a relatively higher local temperature under near-infrared (NIR) laser irradiation, which further triggers a more pronounced enhancement of D-glucose oxidation activity of P-PANI@GOx. Such cascaded chiral effects ultimately endow P-PANI@GOx with enhanced tumor cytotoxic efficacy and immunogenic cell death (ICD)-inducing capability. These findings highlight the crucial influence of chirality-mediated protein adsorption on in vitro antitumor efficacy, shedding light on the rational design of chiral nanomaterials for high-performance biological applications.