Haoming Ding, Xiao Tong, Yong Zhang
MXenes, as a prominent class of two-dimensional (2D) transition metal carbides/nitrides, have attracted extensive attention in innovative biomedical applications due to their distinct layered structure, tunable electronic properties, good biocompatibility, and highly tunable surface/interlayer properties. Their biomedical functionalities largely rely on specific responses to external stimuli, e.g., light, mechanical force, ultrasound waves, magnetism, and heat, which are intrinsically linked to their precise structural design. However, the transition from empirical exploration to rational design of MXene-based nanomedicines is hindered by an insufficient understanding of the relationship between precise structural regulation, stimuli-responsive behavior, and biomedical efficacy. Existing reviews primarily focus on cataloging application scenarios rather than on an in-depth analysis of this core structure-functional relationship. To bridge this critical knowledge gap, this review focuses on the precise control of externally stimuli-responsive MXenes for biomedical applications. It systematically summarizes multi-dimensional structural regulation strategies, including atomic structure modulation, surface chemistry, interlayer engineering, and defect control, and dissects their regulatory effects on stimuli-responsive mechanisms. By integrating representative biomedical applications, a comprehensive structure-response-efficacy framework is established, providing critical theoretical support for the interdisciplinary innovation of materials science and biomedicine. Finally, we propose some challenges and future perspectives relevant to the continuous development of MXenes in biomedicine applications. This review addresses the current research gap and offers practical guidelines for designing smart MXene-based materials, which may promote the transformative potential of structurally engineered MXenes in advancing precision nanomedicine. • Fundamental knowledge of MXene synthesis. • Responsive mechanisms of MXene to different external stimuli based on their biomedical applications. • The strategies to control and optimize the stimuli-responsive behaviors of MXenes. • Diverse biomedical applications of MXenes based on their stimuli-responsive mechanisms.