# Smart nanofluidic systems powered by DNA origami for targeted intracellular delivery: a newer approach

## TL;DR

This review discusses how DNA origami combined with nanofluidics can enable precise, targeted drug delivery inside cells, offering a promising approach for advanced therapies.

## Contribution

The paper introduces smart nanofluidic DNA origami systems as a novel platform for controlled intracellular drug delivery with enhanced precision and adaptability.

## Key findings

- DNA origami structures integrated into nanofluidic systems show superior tumor selectivity and reduced toxicity compared to traditional carriers.
- Stimuli-responsive features like pH-triggered unfolding and enzyme-cleavable hinges enable precise control over drug release.
- AI-assisted design and microfluidic diagnostics are proposed as future directions to enhance the functionality and scalability of these systems.

## Abstract

The convergence of DNA nanotechnology with nanofluidics has catalyzed a transformative shift in precision drug delivery. DNA origami, a self-assembled nanoscale architecture constructed via programmable base pairing, offers atomically precise control over size, shape, and function—making it an ideal scaffold for site-specific therapeutic cargo loading and release. When integrated into nanofluidic systems, these origami nanostructures form intelligent platforms capable of navigating biological barriers, sensing intracellular cues, and delivering payloads in a spatially and temporally controlled manner. This review explores the fabrication principles, design strategies, and intracellular trafficking mechanisms that underpin the efficacy of these smart nanofluidic DNA origami systems. We highlight key stimuli-responsive features such as pH-triggered unfolding, enzyme-cleavable hinges, redox-sensitive disassembly, and light-mediated gate release. Case studies from preclinical models demonstrate their superiority in overcoming drug resistance, enhancing tumor selectivity, and minimizing systemic toxicity compared to conventional nanocarriers. We also evaluate methods for surface modification, channel integration, and stimulus modulation using electron-beam lithography and soft lithography techniques. Additional biosafety and scalability challenges are discussed, alongside regulatory and immunogenicity considerations. The review concludes by outlining future directions involving AI-assisted DNA origami design, microfluidic diagnostics, and digital therapeutics. The synthesis of programmable nanocarriers with smart fluidic control represents a new frontier in targeted therapy, combining modularity, precision, and adaptability. As such, nanofluidic DNA origami systems hold immense promise for next-generation therapeutics in oncology, gene therapy, and personalized medicine, paving the way for dynamic and autonomous intracellular delivery platforms with real-world translational potential.