Framework nucleic acids as programmable carrier for transdermal drug delivery.

Area of Science:

• Biotechnology
• Nanomedicine
• Dermatology

Background:

• DNA nanostructures are promising drug carriers due to biocompatibility and versatility.
• Systemic administration of DNA nanostructures results in rapid serum disintegration and low bioavailability.
• Current limitations hinder the biomedical application of DNA nanostructures as drug delivery systems.

Purpose of the Study:

• To investigate the transdermal delivery of framework nucleic acids (FNAs) via topical application.
• To evaluate the size-dependent penetration of FNAs through skin.
• To assess the efficacy of doxorubicin-loaded FNAs in a mouse melanoma model.

Main Methods:

• Designing FNAs with varying shapes and sizes for skin penetration studies.
• Analyzing skin histology to determine FNA penetration depth.
• Evaluating drug accumulation and tumor inhibition in a mouse melanoma model after topical FNA application.

Main Results:

• FNA penetration into the dermis was size-dependent, with FNAs ≤75 nm showing effective penetration.
• 17 nm tetrahedral FNAs achieved the greatest penetration depth (350 µm).
• Doxorubicin-loaded FNAs demonstrated a ≥2-fold improvement in drug accumulation and tumor inhibition compared to other delivery methods.

Conclusions:

• Framework nucleic acids (FNAs) can be effectively delivered transdermally through topical application.
• FNAs exhibit programmable penetration and maintain structural integrity during skin transit.
• FNAs show significant potential as localized transdermal drug delivery carriers with minimal systemic exposure.