Gene therapy has immense potential as a therapeutic approach to serious diseases. However, efficient delivery and real-time tracking of gene therapeutic agents have not been solved well for successful gene-based therapeutics. Herein we present a versatile gene-delivery strategy for efficient and visualized delivery of therapeutic genes into the targeted nucleus. We developed an integrin-targeted, cell-permeable, and nucleocytoplasmic trafficking peptide-conjugated AIEgen named TD NCP for the efficient and sequential targeted delivery of an antisense single-stranded DNA oligonucleotide (ASO) and tracking of the delivery process into the nucleus. As compared with TD NCP/siRNA-NPs (siRNA functions mainly in the cytoplasm), TD NCP/ASO-NPs (ASO functions mainly in the nucleus) exhibited a better interference effect, which further indicates that TD NCP is a nucleus-targeting vector. Moreover, TD NCP/ASO-NPs showed a favorable tumor-suppressive effect in vivo.
Keywords: AIE luminogens; antisense oligonucleotides; gene delivery; multifunctional peptides; nucleus targeting.
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.