Optically Tunable Catalytic Cancer Therapy Using Enzyme-Like Chiral Plasmonic Nanoparticles

Cascade enzymatic reactions in living organisms are one of the fundamental reaction mechanisms in coordinating various complex biochemical processes such as metabolism, signal transduction and gene regulation. While many studies have attempted to mimic cascade reactions using nanoparticles with enzyme-like activity, there still remains a challenge in developing strategies for the precise tuning of each reaction within complex reaction networks to enhance the catalytic activity. Here, we suggest a novel approach to optically control each stage of the cascade reaction, utilizing orthogonal input of circularly polarized light (CPL), right-handed CPL (RC) and left-handed CPL (LC), coupled with the introduction of chiral plasmonic enzyme-like nanoparticles, which are designed to respond distinctly to RC and LC.<br/>To control the enzymatic activity of nanoparticles depending on the handedness, we took two prominent strategies based on the characteristic features in our chiral plasmonic enzyme-like nanoparticles; 1) generation of hot carriers dependent on CPL, which directly participate in enzymatic reactions and 2) enantioselective interaction with substrate D-glucose, the predominant chiral form of glucose in human body.<br/>Chiral Au nanoparticles (D-Au) and Au-Pd nanoparticles (L-AuPd), which displayed cubic geometries and surfaces oriented in opposite directions, were successfully synthesized through seed-mediated method with introduction of L-/D-GSH ligand during the growth process. D-Au, which has glucose oxidase (GOD)-mimic properties and L-AuPd which mimic peroxidase (POD) reactions respond to RC and LC, respectively, with strong plasmonic effects. By sequentially activating GOD and POD reactions with RC followed by LC, we achieved 1.25- and 1.9-fold enhanced catalytic performance (overall 1.3 times enhancement) compared to non-controlled cascade reactions by creating an optimal acidic environment for the subsequent reaction. Moreover, the D-Au showed a 2-fold higher binding selectivity to the substrates, D-glucose, attributed to chirality matching. In both cellular-level studies and mouse models, the groups irradiated with RC+LC exhibited the highest radical generation and the most efficient cancer treatment outcomes compared to the other irradiation conditions. We believe that our system holds strong potential for practical medical applications, suggesting a promising platform for catalytic therapy.