Self-enhanced copper-doped Prussian blue nanoplatform for amplifying enzyme-like activity and photothermal effects

Chemodynamic therapy (CDT) has emerged as a promising anticancer strategy, yet its therapeutic efficacy is significantly hampered by the elevated glutathione (GSH) levels in the tumor microenvironment (TME) and the limited catalytic efficiency of conventional Fenton reactions. To address these challenges, we developed copper-doped Prussian blue nanoparticles (CPB NPs) for encapsulating curcumin (CUR) and further modified their surface with the active targeting molecule hyaluronic acid (HA), forming CPB@CUR-HA NPs. Notably, this nanoformulation significantly enhances solubility and bioavailability of CUR. In the constructed system, Prussian blue (PB) serves a dual function as an effective photothermal agent: it not only induces tumor cell ablation through photothermal effects but also amplifies CDT efficacy via localized temperature elevation. The incorporated copper ions play crucial roles in depleting excessive GSH and catalyzing Fenton-like reactions, thereby boosting the peroxidase-like activity of PB. Furthermore, copper doping synergistically improves the photothermal conversion efficiency of PB. The mutually reinforcing interplay between CDT and photothermal therapy (PTT), combined with the natural anticancer agent CUR, enables a powerful trimodal therapeutic approach integrating chemotherapy, CDT, and PTT, ultimately achieving remarkable tumor growth inhibition.