Tumor-targeting [2]catenane-based grid-patterned periodic DNA monolayer array for in vivo theranostic application

Area of Science:

• Biotechnology
• Nanotechnology
• Materials Science

Background:

• DNA nanotechnology faces limitations in strand number and targeting for nano-structures.
• Existing DNA nanostructures lack *in vivo* two-dimensional arrays due to technical hurdles.

Purpose of the Study:

• To develop a novel DNA nanostructure for enhanced tumor accumulation and drug delivery.
• To overcome limitations of current DNA nanotechnology for *in vivo* applications.

Main Methods:

• Synthesized a catenane-based grid-patterned periodic DNA monolayer array ([2]GDA) by cross-catenating two palindromic DNA rings.
• Evaluated the *in vivo* stability, cellular uptake, and tumor accumulation of [2]GDA.
• Assessed the therapeutic efficacy of drug-loaded [2]GDA in tumor-bearing animals.

Main Results:

• The [2]GDA demonstrated preferential accumulation in tumor tissues without targeting ligands.
• Its structural flexibility facilitated spherical folding, leading to cellular internalization comparable to commercial lipofectamine 3000.
• [2]GDA exhibited a 360-fold improvement in *in vivo* stability over 24 hours and showed significant therapeutic efficacy with no side effects.

Conclusions:

• The catenane-based DNA array ([2]GDA) presents a stable and effective platform for tumor-targeted drug delivery.
• This nanostructure overcomes key limitations in DNA nanotechnology for *in vivo* applications.
• The [2]GDA shows potential for advanced cancer therapeutics with improved efficacy and safety.