Single-laser excitation synergistic photo- and chemodynamic therapy system based on persistent luminescence nanoparticles

Photodynamic and photothermal therapy (PDT and PTT) have been widely used in tumor treatment researches owe to its advantages of spatiotemporal controlliability and non-invasiveness. Combining two phototherapy strategies together and/or with chemodynamic therapy (CDT) could achieve better therapeutic efficiency, but the resulting inconvenient dual-laser irradiation and the potential skin toxicity limit its development. Moreover, the lack of tumor-specificity causes side-effects to normal tissues. Therefore, shortening the irradiation time, or integrating two lasers, and increasing tumor specificity are necessary to reduce side effects. Herein, we developed a tumor microenvironment responsive one-laser-excited PDT/PTT/CDT synergistic therapeutic nanosystem ZPPSC (refers to ZGGC-PDA-PEI-Si-Pc-Cu) for precise tumor phototherapy. In this nanosystem, the simultaneous PTT and PDT activation using a single laser, enhancing phototherapy efficiency while reducing phototoxicity were achieved. Specifically, persistent luminescence nanoparticle ZnGa1.6Ge0.2O4:Cr (ZGGC) is coated with polydopamine (PDA) through self-polymerization of dopamine, modified with polyethyleneimine (PEI), Si-Pc, and adsorbed with Cu2+. Cu2+ quenches the persistent luminescence (PersL) in physiological environment, and could be reduced to Cu+ under the excess GSH in tumor cells, resulting in removing from nanosystem. Whereafter, PersL is restored, and Fenton-like reaction between Cu+ and overexpressed H2O2 is triggered to generate ·OH for CDT therapy. Under single 808-nm irradiation, PDA will be irradiated to perform PTT, and the opening persistent luminescence could irradiate photosensitizers for PDT and continues to stimulate them even after the laser stops, reducing external excitation time. The in vivo results shown that ZPPSC exhibit ideal PDT performance, and increased local temperature close to 60 °C. Most importantly, the tumor inhibition rate by combined PTT, PDT, CDT with 5-min 808-nm laser irradiation is 99%, and even one mouse was completely cured with the bearing tumor completely disappeared. By using this nanosystem, PDT and PTT were achieved by only on laser with relatively short irradiation time. Moreover, the weak tissue penetration of the 660-nm PS excitation source was also addressed. Our design achieves tumor-specific one-laser three-mode phototherapy with shortened irradiation time, enhancing therapy effectiveness while minimizing side effects. These results exhibit great therapeutic outcomes of ZPPSC for precious tumor phototherapy.