Glutathione-Sensitive Nanoglue Platform with Effective Nucleic Acids Gluing onto Liposomes for Photo-Gene Therapy

Liposomal spherical nucleic acids possess a high density of nucleic acids, e.g., DNA, on a liposomal core. There are two approaches to conjugate DNA onto the zwitterionic liposomes, i.e., covalent and noncovalent conjugation, otherwise using cationic liposomes. However, complex and expensive DNA chemical modification methods need to seek a novel and easy-operating approach to decorating DNA onto liposomes. Inspired by the nanoparticle solution as nanoglues for gels and biological tissues, we use MnO₂ nanosheets to "glue" DNA onto liposomes without DNA modification. In tumor cells with a high glutathione concentration, MnO₂-based nanoglues are degraded, generating water-soluble Mn²⁺ ions, further "unglue" DNA (i.e., DNAzyme), and liposomes. Using the intelligent liposomal nanoglue (DNAzyme/MnO₂/Lip) combining glutathione-sensitive MnO₂ nanosheets, gene silencing agent DNAzyme, and photosensitizer Chlorin e6 (Ce6) in liposomes, effective photo-gene therapy was demonstrated.