Machine Learning Guided Discovery of Superoxide Dismutase Nanozymes for Androgenetic Alopecia

Abstract

Androgenetic alopecia (AGA) is a common form of hair loss, which is mainly caused by oxidative stress induced dysregulation of hair follicles (HF). Herein, a highly efficient manganese thiophosphite (MnPS 3 ) based superoxide dismutase (SOD) mimic was discovered using machine learning (ML) tools. Remarkably, the IC 50 of MnPS 3 is 3.61 μg•mL −1 , up to 12-fold lower than most reported SOD-like nanozymes. Moreover, a MnPS 3 microneedle patch (MnMNP) was constructed to treat AGA that could diffuse into the deep skin where HFs exist and remove excess reactive oxygen species. Compared with the widely used minoxidil, MnMNP exhibits higher ability on hair regeneration, even at a reduced frequency of application. This study not only provides a general guideline for the accelerated discovery of SOD-like nanozymes by ML techniques, but also shows a great potential as a next generation approach for rational design of nanozymes.

Molecular insights of nanozymes from design to catalytic mechanism

“…According to the d-band center theory, the higher in energy of the metal's d-states compared with the Fermi level, the higher the energy of the metal's antibonding states, and hence the stronger the metal's reactivity. In another elegant study, the d-band center was applied to evaluate the OXD-like activity of Pd, Pt, Au, and Ag nanozymes with (111) facets [80]. DFT calculations showed that their d-band centers were −1.8, −2.4, −3.5, −4.1, respectively, which agreed well with the predicted activity order Pd (111)>Pt ( 111)>Au (111), Ag (111).…”

“…To address these "black box"-like tentative exploration, high-throughput computational screening has been successfully applied to discover nanozymes with superoxide-dismutase [109] and hydrolases activity [110]. Very recently, promising methodologies based on machine-learning algorithms have been established to predict efficient nanozymes with high consistency [111,112]. However, there are still challenges with a large amount of allsided experimental data and standards for nanozyme assessment techniques.…”

“…In another elegant study, the d-band center was applied to evaluate the OXD-like activity of Pd, Pt, Au, and Ag nanozymes with (111) facets [80]. DFT calculations showed that their d-band centers were −1.8, −2.4, −3.5, −4.1, respectively, which agreed well with the predicted activity order Pd (111)>Pt ( 111)>Au (111), Ag (111). This work suggests the applicability of the d-band center as a descriptor of the OXD-like activity of metal-based nanozymes.…”

Converting Nanotoxicity Data to Information Using Artificial Intelligence and Simulation

“…More importantly, these newly designed materials were also successfully synthesized and confirmed experimentally. For instance, in a recent study, the DFT-calculated Gibbs reaction-free energy was used to train ML models for screening superoxide dismutase-like nanozyme . Finally, a novel MnPS 3 microneedle patch was discovered and experimentally confirmed to exhibit higher ability on free radical scavenging and hair regeneration.…”

Enhancing Catalytic Activity of a Nickel Single Atom Enzyme by Polynary Heteroatom Doping for Ferroptosis-Based Tumor Therapy

“…Nanozymes, a class of nanomaterials with intrinsic enzyme-mimicking activities, have sparked increasing attention in recent years, which is attributed to their lower cost, superior stability, and tunable catalytic activity as compared to characteristics of their counterparts. − In particular, the nanozymes combining catalytic activities and excellent physical-chemical properties, have widespread applications, from in vitro detection to in vivo treatment. − Despite the impressive progress in nanozyme engineering, the diverse nanostructures, relatively low substrate selectivity, and unsatisfactory atom utilization efficiency significantly hinder their further application. − An emerging generation of nanozymes, called single atom enzymes (SAE), has been exploited for biomedicine and biosensing, owing to their well-defined electronic structures, excellent substrate selectivity, and the highest atom utilization efficiency. − Specifically, the introduction of secondary heteroatom atoms (e.g., phosphorus and sulfur (S)) with lower electronegativity into nitrogen-doped carbon frameworks may regulate coordinated structure evolution of central metal atoms, leading to effectively enhancing the catalytic activity. , However, controllable preparation of single atom enzyme with an expected coordination environment for tumor therapy remains a challenge.…”