Smart Stimuli-Responsive Spherical Nucleic Acids: Cutting-Edge Platforms for Biosensing, Bioimaging, and Therapeutics

Spherical nucleic acids (SNAs) with exceptional colloidal stability, multiple modularity, and programmability are excellent candidates to address common molecular delivery-related issues. Based on this, the higher targeting accuracy and enhanced controllability of stimuli-responsive SNAs render them precise nanoplatforms with inestimable prospects for diverse biomedical applications. Therefore, tailored diagnosis and treatment with stimuli-responsive SNAs may be a robust strategy to break through the bottlenecks associated with traditional nanocarriers. Various stimuli-responsive SNAs are engineered through the incorporation of multifunctional modifications to meet biomedical demands with the development of nucleic acid functionalization. This review provides a comprehensive overview of prominent research in this area and recent advancements in the utilization of stimuli-responsive SNAs in biosensing, bioimaging, and therapeutics. For each aspect, SNA nanoplatforms that exhibit responsive behavior to both internal stimuli (including sequence, enzyme, redox reactions, and pH) and external stimuli (such as light and temperature) are highlighted. This review is expected to offer inspiration and guidance strategies for the rational design and development of stimuli-responsive SNAs in the field of biomedicine.