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

Abstract

Developing non-cationic gene carriers and achieving efficient endo/lysosome escape of functional nucleic acids in cytosol are two major challenges faced by the field of gene delivery.H erein, we demonstrate the concept of self-escape spherical nucleic acid (SNA) to achieve light controlled noncationic gene delivery with sufficient endo/lysosome escape capacity.I nt his system, Bcl-2 antisense oligonucleotides (OSAs) were conjugated onto the surface of aggregationinduced emission (AIE) photosensitizer (PS) nanoparticles to form core-shell SNA. Once the SNAs were taken up by tumor cells,a nd upon light irradiation, the accumulative 1 O 2 produced by the AIE PSs ruptured the lysosome structure to promote OSA escape.P rominent in vitro and in vivo results revealed that the AIE-based core-shell SNAc ould downregulate the anti-apoptosis protein (Bcl-2) and induce tumor cell apoptosis without any transfection reagent.

Recent advances in stimuli‐responsive theranostic systems with aggregation‐induced emission characteristics

“…[ 116 ] In addition, a core‐shell nanostructure (AIE PS as core/Bcl‐2 oligonucleotide [OSA] as shell) for light controlled gene delivery with endo‐/lysosome escape capacity was developed by Liu's group. [ 117 ] Under light irradiation, the core‐shell nanostructure could generate sufficient amount of 1 O 2 to rupture the lysosome structure and let the nanostructure to escape, thus resulting in the released OSA to induce apoptosis of tumor cells.…”

Supramolecular Self‐Assembled DNA Nanosystem for Synergistic Chemical and Gene Regulations on Cancer Cells

“…We proposed that the Te -Mn II coordination complex in the nanosystem might catalyze the production of ROS( mainly in aform of COH) from hydrogen peroxide in lysosome,which facilitated the endo/lysosome escape and improved the delivery efficacyo fs iRNAi nto cytoplasm. [15] ATPr esponsiveness has proven important for rapid release and gene knockdown of siRNAi nc ells. [16] We first evaluated ATPresponsiveness of H2-ssDNA.…”

Synthesis and fundamental studies of a photoresponsive oligonucleotide-upconverting nanoparticle covalent conjugate

“…In fact, there exists a wide variety of commercially available 5 0 -modifiers, such as the GalNAc phosphoramidite (enabling tissue targeting for therapeutic applications) and dye phosphoramidites (to confer fluorescence for diagnostic applications). Lastly, unlike some conjugates that take advantage of stimuli-responsive oligonucleotide release, 59 the current system releases the oligonucleotide without bulky covalent attachments leftover, even with further 5 0 -extension, which could lead to sub-optimal binding affinity with target RNA or protein.…”