Stimuli-responsive structural transformation of adaptive peptide nanomaterials toward biomedical applications

Self-assembling peptide nanomaterials have attracted widespread attention in the biomedical field due to their inherent advantages, such as programmable design, intrinsic bioactivity, and excellent biocompatibility. Especially, peptide nanomaterials can be tailored to possess in vivo microenvironment-responsive morphological characteristics, enabling targeted delivery and enhanced therapy. Herein, this review systematically summarizes in vivo stimuli-responsive morphologically transformable peptide nanomaterials, integrating key biomedical applications, including drug delivery and nanotherapeutics, and emphasizing the structure-activity relationship between morphological transformation and therapeutic efficacy, which is critical for overcoming biological barriers. The responsive design strategies, building blocks, noncovalent interactions, and the responsive nanostructures are discussed. The ability of adaptive morphological changes to overcome multiple biological barriers is highlighted, thereby boosting targeted accumulation, tissue penetration, and therapeutic precision. The challenges and opportunities in developing stimuli-responsive morphologically transformable peptide nanomaterials for biomedical applications are also discussed in depth, providing a deeper insight into the role of smart nanomaterials in improving the efficiency of targeted delivery and therapeutic outcomes.