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

Abstract

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.