Evaluation of the toxicity and efficacy of a multi-target polymer-drug nano-polyplex in SH-SY5Y cells and Drosophila model of tauopathy.

ABSTRACT: Hyperphosphorylated tau contributes to synaptic damage and neuronal dysfunction in neurodegenerative diseases such as Alzheimer's disease (AD), making it a key therapeutic target. This study evaluated the toxicity and therapeutic potential of a novel polymer-drug nano-polyplex, N5NM15, and polyacrylic acid (PAA) in Drosophila tauopathy models and undifferentiated human SH-SY5Y cells. Cellular uptake was demonstrated by N5NM15, and SH-SY5Y cell viability was significantly enhanced (45%, p ≤ 0.0001) under okadaic acid-induced stress, and total tau levels were reduced (1.43-fold, p ≤ 0.01). In comparison, PAA had a modest effect on decreasing tau phosphorylation (1.3-fold) at the pSer202/pThr205 site. Toxicity studies in Drosophila revealed that N5NM15 (3.5:1 and 44:12.5 µg/mL) and PAA (44 µg

SUBMITTER: Mahadik N 

PROVIDER: S-EPMC12606271 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature