An intranasally delivered tetrahedral framework nucleic acid-curcumin nanoassembly (tFNAs-Cur) scavenged reactive oxygen species, reduced infarct volume and improved neurological and behavioral outcomes in MCAO rats via Drd2/β-arrestin2/ERK signaling, with a favorable biosafety profile.
tFNAs-Cur was synthesized by self-assembly and achieved a high curcumin loading efficiency of 87%.
tFNAs-Cur showed potent scavenging activity against multiple reactive oxygen species.
In vitro, tFNAs-Cur reduced oxygen glucose deprivation/reoxygenation (OGD/R)-induced ROS in cytoplasm and mitochondria and improved SH-SY5Y cell function.
Intranasal tFNAs-Cur reduced infarct volume, enhanced neuronal survival, and improved neurological and behavioral outcomes in MCAO rats.
RNA sequencing indicated tFNAs-Cur acts by activating Drd2/β-arrestin2/ERK signaling, improving mitochondrial function and upregulating BDNF.
tFNAs-Cur showed a favorable biosafety profile ex vivo and in vivo.
Stroke injury is made worse when blood flow returns to oxygen-starved brain tissue, triggering a surge of damaging reactive molecules (oxidative stress). Curcumin, the compound in turmeric, can counter this, but the body absorbs it poorly and it struggles to reach the brain. This study packaged curcumin onto a small DNA-based cage-like structure (tFNAs) and delivered it through the nose, a route that can bypass some barriers to the brain. In lab tests the packaged curcumin neutralized several kinds of reactive oxygen molecules and protected cultured nerve-like cells from oxygen and glucose deprivation, helping them survive, grow, and migrate. In rats with an induced stroke, nasal delivery reduced the size of the damaged brain area, preserved more neurons, and improved movement and neurological performance. Gene-activity analysis suggested the effect works through a dopamine receptor-related signaling pathway (Drd2/β-arrestin2/ERK), which improved mitochondrial function and raised levels of BDNF, a protein that supports nerve cells. Safety tests, including blood cell damage tests, blood chemistry and tissue examination, did not show notable problems. This research suggests intranasal antioxidant nanoparticles could be a promising approach for stroke-related reperfusion injury, but the work was done in cells and rats, so its relevance to people remains to be tested in clinical studies.
Li C, Zhao L, Zhang Z, Du Y, Yu J, Yue X, et al.. (2026). Intranasal Delivery of an Antioxidant Nanoassembly for Cerebral Ischemia-Reperfusion Injury via Drd2/β-arrestin2/ERK Signaling.. ACS applied materials & interfaces. https://doi.org/10.1021/acsami.6c16346