A carrier-free DNA nanoplatform for efficient three-in-one tumor therapy in vivo

Drug delivery systems, based on chemical modification and controlled self-assembly of nucleic acid, have played an important role in the treatment of various diseases. Herein, we report a chemically conjugated DNA nanoplatform for efficient three-in-one tumor therapy in vivo. In our design, five copies of hydrophobic chemo-drug (camptothecin, CPT) are conjugated together by a branched organic molecule with an additional arm to introduce a DNA aptamer for targeting (Apt-5CPT). Meanwhile, a photosensitizer (HPPH, for photodynamic therapy) is efficiently organized at the terminal of an antisense oligonucleotide (AS, for gene therapy) to obtain another amphiphilic monomer (HPPH-AS). After co-assembly, a carrier-free DNA nanostructure, with the combination of chemotherapy, photodynamic therapy, and gene therapy, can be efficiently constructed for drug delivery. Under laser irradiation, the generated reactive oxygen species (ROS) can further facilitate their lysosomal escape to achieve subsequent glutathione (GSH)-based drug release for three-in-one tumor therapy in vivo. This rationally developed DNA nanoplatform-based drug delivery system presents a new avenue for the development of tumor therapy.