Case studies of smart nanofluidic DNA origami systems in targeted therapeutic applications.
| Study | Model system | Therapeutic cargo | Delivery strategy | Stimulus trigger | Biological outcome | Key findings |
|---|---|---|---|---|---|---|
| [36] | Orthotopic breast cancer in BALB/c mice | Doxorubicin | MMP-2-responsive DNA origami box integrated in nanofluidic chip | Enzymatic cleavage (MMP-2) | 88% tumor suppression over 21 days | Outperformed liposomal Doxil with reduced cardiotoxicity |
| [37] | Glioblastoma organoids from patient-derived cells | CRISPR-Cas9 (EGFRvIII targeting) | Aptamer-guided DNA origami scaffold for Cas9 delivery | Receptor-mediated endocytosis + passive release | > 90% gene knockout; reduced proliferation | Demonstrated precise gene editing in 3D brain models |
| [38] | B16 melanoma-bearing C57BL/6 mice | Neoantigen + CpG adjuvant | DNA origami vaccine with co-loaded antigen and adjuvant | Immunological activation (APC uptake) | 3-fold increase in IFN-γ release; tumor shrinkage | Induced robust CD8+ T cell-mediated antitumor immunity |
| [39] | A549 lung carcinoma cells (in vitro) | Paclitaxel | Thermo-responsive DNA origami rod | Mild hyperthermia (42°C) | 70% cytotoxicity within 12 h | Controlled intracellular burst release with low off-target effect |
| [40] | HeLa cells (in vitro) | siRNA (Bcl-2 silencing) | UV-light-gated DNA nanocage embedded in a microfluidic chip | UV-triggered gate cleavage | ~75% Bcl-2 mRNA knockdown | Light-activated control over timing and location of gene silencing |
| [41] | MCF-7 breast cancer spheroids | Cisplatin + miRNA-34a | Dual-cargo nanobarrel with GSH-sensitive release | Redox (GSH) | 90% apoptosis in spheroids | Dual-cargo loading of cisplatin and miRNA-34a into a redox-responsive DNA nanobarrel substantially enhances apoptotic activity in 3D MCF-7 tumor spheroids compared to single-agent formulations |
3D: three-dimensional; GSH: glutathione.
DS: Conceptualization, Methodology, Investigation, Writing—original draft, Visualization, Supervision, Project administration. SS: Methodology, Formal analysis, Data curation, Writing—review & editing. NT: Validation, Resources, Writing—review & editing. NB: Supervision, Writing—review & editing, Validation. All authors read and approved the submitted version.
The authors declare that there are no conflicts of interest.
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