A photo-triggerable aptamer nanoswitch for spatiotemporal controllable siRNA delivery

Area of Science:

• Biotechnology
• Nanotechnology
• Molecular Biology

Background:

• Targeted delivery of small interfering RNA (siRNA) is crucial for gene silencing therapies.
• Spatiotemporal control over nucleic acid delivery remains a significant challenge in therapeutic applications.
• Aptamer-based nanodevices offer potential for targeted delivery but require precise regulation.

Purpose of the Study:

• To develop a photo-triggerable aptamer nanoswitch for spatiotemporal regulation of siRNA delivery.
• To investigate the light-induced release mechanism of a photo-labile blocking oligonucleotide.
• To evaluate the efficacy of the nanoswitch for tumor-targeted gene silencing in vitro and in vivo.

Main Methods:

• Design and synthesis of a photo-labile complementary oligonucleotide to block aptamer-nucleolin interaction.
• Construction of an aptamer nanoswitch system for siRNA encapsulation.
• In vitro and in vivo experiments to assess light-triggered release, cellular uptake, and gene silencing efficiency.

Main Results:

• The photo-labile oligonucleotide effectively blocked the binding of the AS1411 aptamer to nucleolin.
• Photo-irradiation successfully reactivated the aptamer-nucleolin recognition, releasing the siRNA.
• Efficient tumor-targeted siRNA internalization and significant gene silencing were observed in vitro and in vivo.

Conclusions:

• A photo-triggerable aptamer nanoswitch provides a viable strategy for spatiotemporal control of siRNA delivery.
• This light-activated system enables precise targeting and efficient gene silencing in tumor models.
• The developed nanoswitch holds promise for advancing targeted nucleic acid therapies.