Light Induced Self-Escape of Spherical Nucleic Acid from Endo/Lysosome for Efficient Non-Cationic Gene Delivery.

Developing non-cationic gene carrier and achieving efficient endo/lysosome escape of functional nucleic acids in cytosol are two major challenges faced by the field of gene delivery. Herein, we demonstrate a concept of self-escape spherical nucleic acid (SNA) to achieve light controlled non-cationic gene delivery with sufficient endo/lysosome escape capacity. In this system, Bcl-2 antisense oligonucleotides (OSAs) were conjugated onto the surface of aggregation-induced emission (AIE) photosensitizer (PS) nanoparticles to form core-shell SNAs. Once the SNAs were uptaken by tumor cells, upon light irradiation, the accumulative 1 O 2 produced by AIE PSs could rupture the lysosome structure to promote OSA escape. Prominent in vitro and in vivo results validated that the AIE based core-shell SNAs could remarkably downregulate the anti-apoptosis protein (Bcl-2) and induce tumor cell apoptosis without any transfection reagent.