Disulfide-Containing Molecular Sticker Assists Cellular Delivery of DNA Nanoassemblies by Bypassing Endocytosis

Abstract

The delivery efficiency of DNA nanoassemblies to the cytosol remains unsatisfactory due to endo- and lysosomal entrapment and degradation, which restricts their bioanalytical and biomedical applications. Herein, the authors developed a disulfide-containing molecular sticker (DSMS) assisted approach to achieve efficient cytosolic delivery of DNA nanoassemblies. DSMS is designed to consist of a disulfide unit for thiol-mediated uptake and a guanidinium cation unit for strongly adhering to DNA nanoassemblies. After attaching with DSMS, a set of DNA nanoassemblies maintained their original three-dimensional features but had a different cellular internalization pathway. These results demonstrated that DSMS-DNA nanoassemblies complex did not enter the cells via endocytosis but instead entered through thiol-mediated direct uptake. Taking advantages of this facile assembly, universal applicability, and direct cytosolic delivery, DSMS might serve as a potent agent to facilitate the applications of DNA nanoassemblies in a variety of fields, such as bioimaging, drug delivery, and gene therapy.