Cu(II)-doped mesoporous polydopamine as biodegradable nanoplatforms for photothermal-enhanced multi-mode anti-tumor therapy

Photothermal effect produced in photothermal therapy (PTT) can not only eradicate tumors but also allow the promotion of biological and chemical reactions in tumor tissues, leading to the potential of photothermal-enhanced anti-tumor therapy with desirable outcomes. Biodegradable polydopamine (PDA) nanoparticles exhibit remarkable photothermal conversion efficiency and stability, making them ideal photothermal agents (PTAs) to achieve photothermal-enhanced anti-tumor therapy. The high affinity of PDA to metal ions provides a broad application prospect for the development of multi-functional nanoplatforms to achieve cancer therapy with high efficacy and specificity. In this work, we fabricated Cu(II)-doped mesoporous PDA nanoparticles with polyethylene glycol (PEG) modified (CMP-P), which not only possessed higher photothermal conversion efficacy than mesoporous PDA nanoparticles, but also presented distinctive self-enhanced chemodynamic (CDT) performance. CMP-P mediated CDT was predicated on catalyzing the Fenton-like reaction to generate hydroxyl radicals (·OH). Impressively, CMP-P further triggered glutathione (GSH) depletion intracellular to prevent the consumption of ·OH, and the photothermal effect further improved ·OH generation. Meanwhile, CMP-P exhibited favorable degradability, the process of which was elaborated intuitively by transmission electron microscope (TEM). CMP-P was then employed for doxorubicin (DOX) loading, and enabled the enhanced DOX release in-situ under the stimulation of photothermal effect and tumor micro-environment (TME). The lower IC50 value of DOX/CMP-P (1.68 μg/mL) than the signal therapy suggested the superior synergistic effect of DOX/CMP-P. Meanwhile, in vivo experiments also revealed the considerably improved anti-tumor efficacy of synergistic therapy mediated by DOX/CMP-P.