Jantrania, K. | bioRxiv Science

bioRxiv2026

Programmable DNA Nanocages Enhance Levodopa Delivery for Neuroprotection in a Zebrafish Model of Parkinson's Disease

Parkinsons Disease (PD) is the second-most prevalent neurodegenerative disease, often characterized by neural motor dysfunction, oxidative stress, and dopamine receptor malfunction leading to improper dopamine levels in the system. DNA tetrahedron nanostructures are a promising drug delivery agent due to their biocompatibility and properties of controlled and sustained release. In this study we evaluated the potential of using TD-mediated Levodopa delivery for a MPTP induced Parkinsons Disease model in Zebrafish larvae. The induction of Parkinsonism led to morphological behaviour changes like the presence of tremors, erratic swimming behaviour, latency, and reduced locomotor activity, even elevated reactive oxygen species (ROS) and apoptosis was observed. These effects and symptoms were alleviated when the larvae were treated using TD:Levodopa conjugates, particularly at the 1:100 ratio. At the molecular level, genes like TH, DAT, SOX2, PARKIN and apoptotic genes like BCL2 and caspases showed alteration in expression in the Parkinsonism model and post treatment was induced. This highlights the potential of using DNA nanocages as a novel drug delivery agent as therapeutic strategy for Parkinsons disease. TOCDopamine loaded DNA nanocages with the capacity to overcome biological barriers for release of dopamine with neuroprotection activity in Parkinsons disease model of zebrafish. O_FIG O_LINKSMALLFIG WIDTH=193 HEIGHT=200 SRC="FIGDIR/small/742731v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1d2b94eorg.highwire.dtl.DTLVardef@183bc1aorg.highwire.dtl.DTLVardef@1b254ddorg.highwire.dtl.DTLVardef@e1b589_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

DNA Nanocage-Mediated Aspirin Delivery Mitigates Excitotoxicity and Promotes Neuroprotection in Ischemic Stroke-Induced Zebrafish

Oxidative stress, apoptosis, excitotoxicity, and compromised neuronal function are the hallmarks of ischaemic stroke, a major cause of neurological impairment. Because of their controlled-release properties and biocompatibility, DNA tetrahedron nanostructures (TD) offer a viable platform for targeted drug delivery. In this work, we used a zebrafish larval model of ischaemic stroke to assess the neuroprotective potential of TD-mediated aspirin administration and investigated the TD:Aspirin complexation modes using molecular dynamics (MD) simulations. In addition to morphological abnormalities, elevated reactive oxygen species (ROS), thrombus formation, intracellular calcium accumulation, and dysregulated expression of neuroprotective and apoptotic genes, stroke induction resulted in significant behavioural deficits, including decreased locomotor activity, increased latency, and erratic swimming. Treatment with TD:Aspirin, especially at a 1:100 ratio, markedly improved locomotor behaviour, restored production of BDNF, GDNF, MBP, -tubulin, GRIN2B, SLC8A, NOS1, and caspases, normalised heart rate, lowered ROS generation and apoptosis, and decreased thrombus and calcium deposition. TD:Aspirin showed better efficacy than free Aspirin and TD-only groups, perhaps as a result of improved stability, bioavailability, and sustained release. These results demonstrate the potential of drug delivery via DNA nanocages as a novel therapeutic approach for ischaemic stroke, offering neuroprotection, functional recovery, and neuronal homeostasis restoration. TOC GraphicDNA Nanocage-Mediated Aspirin Delivery Mitigates Excitotoxicity and Promotes Neuroprotection in Ischemic Stroke-Induced Zebrafish O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/696221v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@18dd327org.highwire.dtl.DTLVardef@21b8b4org.highwire.dtl.DTLVardef@1e53283org.highwire.dtl.DTLVardef@5771e6_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗