Advantages and limitations of DNA origami-nanofluidic platforms versus traditional nanocarriers.
| Feature | DNA origami-nanofluidic systems | Traditional nanocarriers (liposomes, polymers, dendrimers, etc.) | Commentary |
|---|---|---|---|
| Structural precision | Nanometer-scale programmable architecture (1–2 nm resolution) | Limited geometric control; dependent on self-assembly or bulk properties | DNA origami offers atomic-level customizability not achievable in conventional carriers |
| Cargo loading specificity | Precisely addressable sites; multiplexed cargo placement | Nonspecific encapsulation; batch-to-batch variability | Origami allows for stoichiometric and directional loading |
| Stimuli responsiveness | Highly tunable: pH, redox, enzyme, light, thermal, electric field | Limited to pH, enzyme, and sometimes redox | Origami systems integrate complex logic-based responsiveness |
| Biocompatibility and degradability | High; composed of natural DNA; easily metabolized | Variable; dependent on material (e.g., PEG, PLGA, chitosan) | DNA origami generally elicits lower inflammatory responses |
| Intracellular targeting | Site-specific via aptamers, DNAzymes, logic gates | Targeting via antibodies, peptides, or the passive EPR effect | Origami allows AND/OR gate logic for precise cell type recognition |
| Fabrication scalability | Limited; costly oligonucleotide synthesis and thermal folding | High; scalable emulsification and self-assembly | A key limitation for origami platforms in clinical translation |
| Stability in physiological conditions | Susceptible to nuclease degradation without modifications | Generally stable depending on lipid/polymer coating | Chemical modifications (e.g., PEGylation) improve origami performance |
| Endosomal escape efficiency | Moderate; dependent on auxiliary strategies (e.g., fusogenic peptides) | Often enhanced via pH-sensitive polymers or ionizable lipids | Both require additional design elements for efficient cytosolic delivery |
| Immunogenicity | Low to moderate (sequence- and CpG-dependent) | Variable; can induce cytokine release or complement activation | CpG content and repetitive motifs in DNA origami require optimization |
| Clinical translation readiness | Emerging; preclinical proof-of-concept demonstrated | Advanced; several platforms FDA-approved (e.g., liposomes) | Origami-nanofluidics are still in early translational stages |
EPR: enhanced permeability and retention; PEG: polyethylene glycol.