Programmable Assembly of Multivalent DNA-Protein Superstructures for Tumor Imaging and Targeted Therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Programmable DNA materials offer promise in research but face challenges in synthesis, stability, and targeting for clinical use.
• Current limitations hinder the translation of DNA-based therapeutics into effective treatments.

Purpose of the Study:

• To develop a novel DNA-protein superstructure for targeted drug delivery.
• To enhance stability, targeting efficacy, and therapeutic outcomes for cancer treatment.

Main Methods:

• One-pot biomimetic assembly of programmable DNA wires into DNA nanospheres using protamine.
• Encoding nanostructures with varying types and densities of aptamers for multivalent cell targeting.
• Evaluation in subcutaneous and orthotopic non-small-cell lung cancer murine models.

Main Results:

• Achieved high affinity and stability of DNA-protein nanospheres for targeted therapy.
• Demonstrated high cancer cell selectivity and reduced side effects.
• Showcased excellent therapeutic efficacy and sensitive tumor imaging in preclinical lung cancer models.

Conclusions:

• The biomimetic assembly approach yields practical DNA nanomaterials for targeted therapy.
• This method offers a promising platform for advancing oligonucleotide drug delivery and clinical translation.