DNA-Responsive SiO₂ Nanoparticles, Metal-Organic Frameworks, and Microcapsules for Controlled Drug Release

Recent advances addressing the development of stimuli-responsive nucleic acid (DNA)-functionalized micro/nanocarriers for the controlled release of drugs are presented. The DNA associated with the drug-loaded carriers acts as capping units that lock the drugs in the carriers. In the presence of appropriate triggers, the capping units are unlocked, resulting in the release of the drugs. Three types of DNA-modified carriers are discussed, including mesoporous SiO₂ nanoparticles (MP SiO₂ NPs), metal-organic framework nanoparticles (NMOFs) and micro/nanocapsules. The triggers to unlock the DNA gating units include pH, the dissociation of K⁺-stabilized G-quadruplexes in the presence of crown ethers, the catalytic dissociation of the capping units by enzymes or DNAzymes, the dissociation of capping units by the formation of aptamer-ligand complexes (particularly ligands acting as biomarkers for different diseases), and the use of light for the photochemical unlocking of the DNA gates. Different issues related to the targeting of the different drug-loaded carriers to cancer cells, the switchable ON/OFF release of the drug loads, and the selective cytotoxicity of the drug-loaded carriers toward cancer cells are discussed. Finally, the future perspectives of the stimuli-responsive DNA-based, drug-loaded micro/nanocarriers for future nanomedicine and, in particular, the development of autonomous sense-and-treat systems are addressed.