Synthesis and Applications of Stimuli‐Responsive DNA‐Based Nano‐ and Micro‐Sized Capsules

Abstract Stimuli‐responsive, drug‐loaded, DNA‐based nano‐ and micro‐capsules attract scientific interest as signal‐triggered carriers for controlled drug release. The methods to construct the nano‐/micro‐capsules involve i) the layer‐by‐layer deposition of signal‐reconfigurable DNA shells on drug‐loaded microparticles acting as templates, followed by dissolution of the core templates; ii) the assembly of three‐dimensional capsules composed of reconfigurable DNA origami units; and iii) the synthesis of stimuli‐responsive drug‐loaded capsules stabilized by DNA−polymer hydrogels. Triggers to unlock the nano‐/micro‐capsules include enzymes, pH, light, aptamer−ligand complexes, and redox agents. The capsules are loaded with fluorescent polymers, metal nanoparticles, proteins or semiconductor quantum dots as drug models, with anti‐cancer drugs, e.g., doxorubicin, or with antibodies inhibiting cellular networks or enzymes over‐expressed in cancer cells. The mechanisms for unlocking the nano‐/micro‐capsules and releasing the drugs are discussed, and the applications of the stimuli‐responsive nano‐/micro‐capsules as sense‐and‐treat systems are addressed. The scientific challenges and future perspectives of nano‐capsules and micro‐capsules in nanomedicine are highlighted.