H₂O₂-responsive polysaccharide-POSS electrochemical nanosystem for targeted thyroid cancer therapy

Thyroid cancer remains difficult to treat due to poor prognosis and drug resistance. Germacrone, a sesquiterpenoid from Curcuma longa, exhibits antitumor activity by modulating the PI3K/AKT-FOXO3 pathway. Here, we developed a responsive drug delivery system (1-CS-2-POSS@Germacrone) by modifying carboxymethyl chitosan (CMCS) with conjugated units (compound 1) and Jasminum sambac extract (compound 2), and stabilizing it with polyhedral oligomeric silsesquioxane (POSS). This design enhanced structural integrity, drug-loading efficiency, and electron conductivity for light-triggered release. FTIR and PXRD confirmed successful Germacrone loading via chemical and physical interactions. The bandgap narrowed from 2.43 eV to 2.26 eV, and the valence band shifted to 2.71 eV, indicating improved redox potential. EIS and photocurrent tests showed superior charge transport. Under 420 nm light, 9.1 μmol of Germacrone was released in 60 min with high reproducibility and an AQY of 4.12 %. Release was O₂-dependent, decreasing sharply under N₂. EPR and RRDE revealed a dominant 2e^- ORR pathway with >90 % H₂O₂ selectivity, facilitating ROS-driven release. In vitro, the system inhibited BCPAP thyroid cancer cell proliferation and upregulated FOXO3, offering a promising strategy for precision therapy.