Carrier-Free Hybrid DNA Nanoparticles for Light-Induced Self-Delivery of Functional Nucleic Acid Enzymes
Leilei Shi, Wenbo Wu, Yukun Duan, Li Xu, Sha Li, Xihui Gao, Bin Liu
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.