A Reconfigurable DNA Framework Nanotube-Assisted Antiangiogenic Therapy.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Antiangiogenic therapy faces limitations due to off-target effects causing organ injury.
• Effective delivery and controlled release of antiangiogenic agents to tumors are critical for clinical success.

Purpose of the Study:

• To develop a smart DNA-based nanodrug (Endo-rDFN) for targeted delivery and controlled release of endostar (Endo).
• To evaluate Endo-rDFN's efficacy in inhibiting angiogenesis and tumor growth while minimizing off-target organ damage.

Main Methods:

• Assembling endostar (Endo) into a reconfigurable DNA framework nanotube (rDFN) to create Endo-rDFN.
• Utilizing the AS1411 DNA aptamer for recognition of tumor-overexpressed nucleolin for targeted delivery.
• Assessing tumor targeting, controlled release, anti-angiogenic effects, tumor growth inhibition, and organ protection in vivo.

Main Results:

• Endo-rDFN demonstrated enhanced tumor targeting and accumulation of Endo in tumor tissues.
• On-demand release of Endo was achieved at tumor sites via nucleolin recognition.
• Significant inhibition of angiogenesis and tumor growth was observed.
• Endo-rDFN provided protection against multiorgan injury without compromising organ function.

Conclusions:

• Reconfigurable DNA framework nanotubes (rDFN) are promising vectors for reducing antiangiogenic therapy-induced multiorgan injury.
• Endo-rDFN highlights the potential of smart nanodrugs for safer and more effective clinical application of antiangiogenic agents.