Novel Tumor-Microenvironment-Based Sequential Catalytic Therapy by Fe(II)-Engineered Polydopamine Nanoparticles.

Traditional tumor treatments suffer from severe side effects on account of their invasive process and inefficient outcomes. Featuring a unique physical microenvironment, the tumor microenvironment (TME) provides a new research direction for designing more efficient and safer treatment paradigms. In this study, we fabricated a polydopamine (PDA)-based TME-responsive nanosystem, which successfully integrates glucose degradation, the Fenton reaction, and photothermal therapy for efficient cancer therapy. Through a convenient hydrothermal method, Fe2+-doped Fe(II)-PDA nanoparticles were successfully fabricated, which show an excellent photothermal effect and interesting reactivity for the Fenton reaction. Instead of introducing toxic anticancer agents, natural glucose oxidase (GOD) was grafted on Fe(II)-PDA, forming a cascade catalytic nanomedicine for a specific response to the glucose in TME. GOD grafted on Fe(II)-PDA-GOD is ought to catalyze abundant glucose in TME into gluconic acid and H2O2. The concomitant generation of H2O2 can enhance the efficiency of the sequential Fenton reaction, producing abundant hydroxyl radicals (•OH) for cancer therapy. Besides, the overconsumption of intratumoral glucose also could inhibit tumor growth by reducing the energy supply. Taken together, the in vitro and in vivo antitumor studies of such TME-based Fe(II)-PDA-GOD nanosystems displayed a favorable synergistic potency of glucose degradation, the Fenton reaction, and photothermal therapy against tumor growth. Our design expands the biological application of multifunctional PDA while providing novel strategies toward effective antitumor treatment with minimal side effects.