The Hydrophobicity of AIE Dye Facilitates DNA Condensation for Carrier‐Free Gene Therapy

Abstract A nanomaterial with a high payload of nucleic acid drugs and low cytotoxicity is desirable for gene therapy. Herein, a new DNA assembly method triggered by hydrophobic interaction and strengthened by Mg 2+ electrostatic interaction for carrier‐free gene transfection is reported. It is discovered that a hydrophobic aggregation‐induced emission dye with a low molecular weight that is modified to an oligonucleotide will greatly change the condensation properties of DNA. The conditions and the possible mechanism of such an aggregation process are carefully investigated. Further, it is revealed that the resultant aggregate is suitable for gene delivery, as in which the oligonucleotides are protected from degradation, and the intracellular permeability is enhanced. For the delivery of Bcl‐2 antisense oligonucleotide, such a system exhibits a high gene transfection efficiency both in vitro and in vivo. Accordingly, an interesting observation is reported in this study that an aggregation‐induced emission dye with a molecular weight much lower than the nucleic acid drugs can cause oligonucleotide aggregation and facilitate gene transfection. Such a delivery system provides a practical and inspiring example for the development of gene therapy in the future.