Turmeric-Derived Exosome-Like Nanoparticles Inhibit Non-Small Cell Lung Cancer via Epigenetic Regulation.

[BACKGROUND] Turmeric-derived exosome-like nanoparticles (TELNs) are nanoscale vesicles of plant origin with therapeutic potential. However, the specific efficacy and mechanisms of TELNs in inhibiting non-small cell lung cancer (NSCLC) remain unclear. This study investigated the effects of TELNs on NSCLC by epigenetically regulatiing histone acetyltransferase human males absent on the first (hMOF) and histone H4K16 acetylation (H4K16ac).

[METHODS] TELNs were isolated from turmeric using differential centrifugation and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and zeta potential measurements. Cellular uptake was assessed via PKH26 labeling. assays evaluated the effects of TELNs on apoptosis (annexin V/PI staining, JC-1 mitochondrial depolarization, caspase-3 cleavage) and proliferation (CCK-8). The efficacy of TELNs was examined in A549 xenografts. Bioinformatics and molecular docking analyses revealed the interaction of curcumin in TELNs with hMOF, while RNA interference validated the role of hMOF in TELN-mediated apoptosis and migration suppression.

[RESULTS] TELNs exhibited exosome-shaped morphology and efficient uptake by A549 cells. Treatment with TELNs induced apoptosis and reduced tumor volume by 58.1%. Mechanistically, TELNs upregulated hMOF expression and H4K16ac levels. RNA interference confirmed that knockdown of hMOF weakened the effect of the TELNs. Molecular docking suggested curcumin in TELNs may interact with hMOF.

[CONCLUSION] This study reveals a novel epigenetic mechanism wherein TELNs suppress NSCLC by activating hMOF/H4K16ac. Curcumin within TELNs increases hMOF levels, thus positioning TELNs as a potential nanotherapeutics with the capacity for epigenetic modulation. Our findings underscore the potential of TELNs in NSCLC treatment and highlight hMOF as a therapeutic target.