Glutathione-Responsive DNA-Based Nanocontainers Through an Interfacial Click Reaction in Inverse Miniemulsion

The synthesis of nanoscale biocompatible carriers that are able to release encapsulated material within an intracellular environment in a controlled way still remains a challenge. Hereby, the synthesis of a new class of DNA-based nanocontainers having a glutathione-cleavable shell is described. These containers are able to break in response to the presence of intracellular specific tripeptide glutathione in the surrounding medium. The formulation of nanocontainers in the size range between 190 and 220 nm is achieved through the interfacial thiol-disulfide exchange reaction between dithiol DNA oligonucleotides (20 bases) and disulfide groups of a comonomer in inverse miniemulsion. DNA containers with different disulfide moieties are synthesized by taking different ratios of a dimaleimide-based fluorescent BODIPY dye and the disulfide monomer, which form the shell through the interfacial click of the thiol-ene reaction and the dithiol exchange reaction of the glutathione-cleavable disulphide comonomer. The disruption kinetics of the shell upon addition of glutathione into the dispersion are investigated by isothermal titration calorimetry (ITC). Cleavage of the nanocontainer's shell containing fluorescent BODIPY dye is confirmed by fluorescence correlation spectroscopy (FCS). It is believed that the obtained nanocontainers have great potential as smart nanocarriers in biosensor and therapeutic applications.