ArticleMaterials today. Bio2026
Intranasal L-DOPA/TPP-engineered extracellular vesicles deliver icariin to ameliorate mitochondrial dysfunction with associated sphingolipid remodeling in Alzheimer's disease models.
Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is associated with mitochondrial dysfunction, oxidative stress, and disrupted lipid homeostasis, but the therapeutic translation of mitochondrial-protective agents remains limited by inefficient brain delivery, insufficient neuronal selectivity, and poor subcellular precision. Here, we developed an intranasal extracellular vesicle formulation (L-DOPA/TPP-EV-ICA) by loading icariin (ICA) into mesenchymal stem cell-derived extracellular vesicles and post-inserting DSPE-PEG-Levodopa and TPP-PEG-PE to enhance nasal environment, neuronal association, and mitochondria-associated intracellular enrichment. The engineered vesicles retained EV-like morphology, showed measurable ICA encapsulation, and maintained colloidal stability under the tested storage and simulated nasal conditions. In a human nasal epithelial Transwell model, L-DOPA/TPP-EV-ICA showed greater neuronal uptake than unmodified EVs without detectable disruption of epithelial barrier integrity and exhibited preferential colocalization with mitochondria-associated structures after cellular internalization. In Aβ-injured neuronal cells, L-DOPA/TPP-EV-ICA treatment reduced mitochondrial oxidative stress and mPTP opening, improved membrane potential, and enhanced ATP production and redox-related parameters. Following intranasal administration, the engineered formulation generated stronger and more persistent brain-associated fluorescence and showed preferential association with NeuN-positive cells. In APP/PS1 mice, treatment improved cognitive performance, and attenuated histopathological and mitochondrial abnormalities. Integrated proteomic, metabolomic analyses, and protein-level analyses further identified treatment-associated alterations in sphingolipid-related pathways. These findings support L-DOPA/TPP-EV-ICA as a promising preclinical intranasal EV platform for improving mitochondrial function and modulating sphingolipid-associated alterations in AD-related models.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.