Cobalt-doped polydopamine combined with glucose oxidase for enhanced mild photothermal therapy with starvation therapy

Although photothermal therapy (PTT) has been deemed as an effective approach for tumor ablation, the ubiquitous overheat over 50 °C in the PTT process would damage surrounding normal tissue. The combination of nutrient depletion at the tumor site with mild PTT seems like an efficient way to overcome this dilemma. In this work, cobalt-doped polydopamine (CP) behaved as both photothermal agent and glucose oxidase (GOx) carrier to achieve a starvation assisted photothermal therapy. CP possesses more weak acid sites than pure polydopamine, and it gives higher encapsulation efficiency and loading capacity of 89.71% and 47.29% towards GOx, respectively. The CPGP was prepared by coating the GOx-loaded CP with a phase change material (PCM) layer. The solidified PCM prevents the binding between the GOx and glucose, thereby inhibiting GOx activity. The PCM melts at 45 °C and then the GOx activity restores to normal level. The CPGP could cause reduction of intracellular levels of NAD⁺, NADH and ATP, as well as mitochondrial dysfunction and the induction of apoptosis or necrosis. Hence, CPGP-mediated starvation-photothermal combination therapy exhibits an effective tumor-killing effect. In addition, upregulated M1-polarized macrophages, CD4⁺ T cells and CD8⁺ T cells were observed in the mouse model.