Enzyme-driven micro- and nanomotors: Design, construction and biological applications

Enzyme-powered micro/nanomotors (EMNMs) are a type of self-propelled devices that biologically convert chemical energy into mechanical work through enzyme-catalyzed reactions. Compared to conventional chemically driven counterparts, a significant advantage of these platforms lies in their utilization of endogenous substrates, such as glucose, urea, glycerides, and peptides, to achieve autonomous propulsion. Through the rational design and regulation of functional material components, EMNMs can efficiently perform tasks ranging from active target recognition to autonomous drug loading and controlled release for biomedical applications. Additionally, emerging therapeutic modalities, such as photothermal and starvation therapy integrated with EMNMs, have been extensively investigated for diverse clinical interventions. Up to date, several reviews have outlined general progress in the field, however, a comprehensive synthesis of fabrication strategies and their specific therapeutic applications remain relatively underexplored. To address this gap, this review comprehensively elucidates the design principles and construction strategies of EMNMs through enzyme selection, matrix materials, and morphological structures. Besides, the latest research advances in treating cardiovascular and cerebrovascular diseases, cancer, and urological disorders were also systematically summarized. Through further analyzing current bottlenecks and outlines future directions, this article might aim to providing a cornerstone reference and strategic guidance for future endeavors of EMNMs in related fields. STATEMENT OF SIGNIFICANCE: ∙The core design principles and fabrication methodologies of enzyme-powered micro/nanomotors (EMNMs) are comprehensively elucidated. ∙Systematic structure-activity correlations of EMNMs are established across three pivotal dimensions: enzyme screening, matrix scaffolds and morphological architectures. ∙State-of-the-art advances of EMNM platforms for therapeutic intervention against malignancies, cardiovascular and cerebrovascular pathologies, and urinary tract disorders are thoroughly summarized.