Carrier-Free Hybrid DNA Nanoparticles for Light-Induced Self-Delivery of Functional Nucleic Acid Enzymes

Abstract

Herein, we developed hybrid DNAzyme nanoparticles (NPs) to achieve light-induced carrier-free self-delivery of DNAzymes with sufficient cofactor supply and lysosome escape capacity. In this system, aggregation-induced emission (AIE) photosensitizer (PS) (TBD-Br) was grafted onto a phosphorothiolated DNAzyme backbone, which automatically self-assembled to form NPs and the surface phosphorothioate group could easily coordinate with the cofactor Zn²⁺ in the buffer. When the yielded hybrid DNAzyme NPs were located inside tumor cell lysosomes, the ¹O₂ from TBD-Br under light illumination could destroy lysosome structure and promote the Zn²⁺ coordinated DNAzyme NPs escape. Both in vitro and in vivo results demonstrated that the hybrid DNAzyme NPs could downregulate the early growth response factor-1 protein (EGR-1) to inhibit tumor cell growth in addition to induce tumor cell apoptosis by AIE PS (TBD-Br) under light irradiation.