Smart materials, often described as intelligent or stimuli-responsive systems, have emerged as a cornerstone in the design of next-generation micro- and nanodevices for biomedical use. For such applications, biocompatibility is paramount, and enzymes—owing to their exceptional catalytic properties—offer a compelling route for material design. Enzyme-based smart materials enable bidirectional communication between biological environments and engineered systems, mimicking the dynamic interplay found in natural biological structures. Two primary strategies have been identified: constructing materials directly from enzymes, and creating materials that respond selectively to enzymatic activity.
The utility of enzymes in these contexts hinges on their ability to retain high catalytic efficiency under operational conditions. Yet, their inherently fragile nature makes them susceptible to denaturation or destabilization in harsh environments, shortening functional lifespan and increasing costs. One area of focus has been bio-enzymes encoded by antibiotic resistance genes (ARGs). Qi et al. examined the distribution of 28 ARGs and eight heavy metals in dairy farm soil using geographic information system techniques, revealing correlations between heavy metal content and ARG abundance. This work sheds light on how environmental factors influence enzyme activity, with implications for both agricultural and biomedical systems.
Enhancing enzyme stability and performance has long relied on immobilization techniques. Yuan et al. demonstrated that lysozyme immobilized on ZnO nanoparticles produced synergistic antibacterial effects against *Escherichia coli* and *Staphylococcus aureus*. The mechanism involved reactive oxygen species generation, and the composite outperformed either pure ZnO nanoparticles or pure lysozyme in both in vitro and in vivo studies.
Hydrogels present another promising substrate for enzyme loading. Yao et al. engineered an alginate hydrogel loaded with ClyC (ClyC-AH) to deliver sustained antibacterial action against *Staphylococcus aureus*. The hydrogel maintained ClyC stability and activity over extended periods, improving biocompatibility and therapeutic duration compared to the enzyme alone.
Beyond immobilization, researchers have turned to nanomaterials with intrinsic enzyme-like properties—nanozymes. These synthetic constructs offer high stability, tunable activity through control of size, structure, and composition, and ease of preparation and storage. Nanozymes are classified into metal-oxide, noble metal, and carbon-based categories, each with distinct advantages. Wang et al. summarized their applications in biosensing, therapy, antibacterial strategies, and anti-inflammatory treatments.
Metal-related nanozymes, such as Pd-Ir systems, excel in bioanalysis. However, fabricating Pd-Ir nanocubes with atomic-thickness Ir shells poses a challenge due to the low energy barrier for homogeneous nucleation of Ir atoms. Li et al. addressed this by synthesizing such nanocubes in aqueous solution at room temperature, enabling biomolecules to access the Pd-Ir surface. These structures exhibit strong peroxidase activity and fluorescence quenching, positioning them as valuable tools for clinical biosensing.
Carbon-based nanozymes offer a different set of benefits: excellent water dispersion, chemical inertness, resistance to photobleaching, and versatile surface engineering. Jin et al. reviewed their use in biomedicine, catalysis, and biosensing, highlighting their potential to overcome the rapid inactivation that plagues natural enzymes.
Smart materials responsive to enzymes incorporate two critical components: an enzyme-sensitive element, such as a substrate or mimic, and a mechanism to control material transformation. These systems exploit the selectivity and mild operating conditions of enzymatic reactions, aligning with key biological pathways in health and disease. In photodynamic therapy (PDT), for example, reactive oxygen species generated by photosensitizers can destroy tumor cells. Yet, non-specific distribution of photosensitizers risks damaging healthy tissue. Liu et al. reviewed enzyme-responsive smart materials tailored to the enzymatic environment of tumors, enabling targeted drug delivery, enhancing therapeutic outcomes, and minimizing side effects. Such strategies hold promise for advancing PDT in malignancy treatment.