Cascade enzymatic reactions in living organisms are one of the fundamental mechanisms in coordinating various biochemical processes such as metabolism and signal transduction. Despite many attempts to mimic cascade reactions using nanoparticles(NPs) with enzyme-like activity, it still remains a challenge in precise tuning of each reaction within complex networks. Here, we suggest a novel approach to optically control each stage of 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 NPs, which are designed to respond distinctly to RC and LC.

To control the enzymatic activity of NPs based on handedness, two key strategies were employed; 1) generation of hot carriers dependent on CPL and 2) enantioselective interaction with D-glu, the dominant chiral form of glucose in human body.

Chiral Au NPs (D-Au) and Au-Pd NPs (L-AuPd) were synthesized using L-/D-GSH ligand. D-Au, mimicking glucose oxidase (GOD), and L-AuPd, mimicking peroxidase (POD), respond to RC and LC, respectively, with strong plasmonic effects. By sequentially activating GOD and POD reactions with RC followed by LC, the catalytic performance was enhanced by 1.25- and 1.9-fold compared to uncontrolled reactions by creating an optimal acidic environment for the subsequent reaction. Moreover, the D-Au showed a 2-fold higher binding selectivity to the D-glucose, due to chirality matching. In both cellular studies and mouse models, the RC+LC irradiation group exhibited the highest radical generation and the most effective cancer treatment 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.

<b>Fig 1. </b>(a) Cascade enzymatic reaction of chiral plasmonic nanoparticles for cancer treatment under RC and LC illumination. (b) TEM image and (c) CD spectra of D-Au and L-AuPd. (d) Plasmon-enhanced enzymatic activity of D-Au and L-AuPd under RC and LC. (e) Enantioselectively enhanced substrate selectivity according to the chirality of gold nanoparticle.

Fig 1. (a) Cascade enzymatic reaction of chiral plasmonic nanoparticles for cancer treatment under RC and LC illumination. (b) TEM image and (c) CD spectra of D-Au and L-AuPd. (d) Plasmon-enhanced enzymatic activity of D-Au and L-AuPd under RC and LC. (e) Enantioselectively enhanced substrate selectivity according to the chirality of gold nanoparticle.

Ryeong Myeong Kim

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