A Multifunctional Peptide-Conjugated AIEgen for Efficient and Sequential Targeted Gene Delivery into the Nucleus

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Gene Therapy

Background:

• Gene therapy holds significant therapeutic potential but faces challenges in efficient delivery and real-time tracking of agents.
• Nucleus-targeted delivery is crucial for many gene-based therapeutics, especially those involving nucleic acids like antisense oligonucleotides.

Purpose of the Study:

• To develop a versatile gene delivery strategy for efficient, visualized, and nucleus-targeted delivery of therapeutic genes.
• To create a novel peptide-conjugated aggregation-induced emission gen (AIEgen) for tracking gene delivery processes.
• To evaluate the efficacy of the developed system for delivering antisense single-stranded DNA oligonucleotides (ASOs) and its therapeutic potential.

Main Methods:

• Development of an integrin-targeted, cell-permeable, and nucleocytoplasmic trafficking peptide-conjugated AIEgen (T_D NCP).
• Utilized T_D NCP for the targeted delivery of antisense single-stranded DNA oligonucleotides (ASOs) encapsulated in nanoparticles (NPs).
• Compared the gene silencing efficacy of T_D NCP/ASO-NPs with T_D NCP/siRNA-NPs and assessed in vivo tumor suppression.

Main Results:

• T_D NCP facilitated efficient and visualized delivery of ASOs into the nucleus.
• T_D NCP/ASO-NPs demonstrated superior interference effects compared to T_D NCP/siRNA-NPs, confirming nucleus-targeting capability.
• T_D NCP/ASO-NPs exhibited a significant tumor-suppressive effect in vivo.

Conclusions:

• The developed T_D NCP system is a versatile and effective nucleus-targeting vector for gene therapy.
• This strategy enables efficient delivery and real-time tracking of therapeutic genes, addressing key challenges in gene-based therapeutics.
• The system shows promise for in vivo therapeutic applications, including tumor suppression.