Multishell Nanoparticles with “Linkage Mechanism” for Thermal Responsive Photodynamic and Gas Synergistic Therapy

The strategies of combining photodynamic therapy (PDT) with other therapeutics are considered to be the most suitable methods in improving the antitumor therapeutic efficiency. Herein, a “Linkage Mechanism” strategy based on thermal controllable multishell nanoparticles (CuS@SiO₂-l-Arg (l-arginine)@PCM (phase-change material)-Ce6 (chiorin e6)) is proposed for combing PDT and NO-based gas therapy. Upon 1060 nm laser irradiation, the PCMs will melt under the photothermal effect induced by CuS and the loaded Ce6 and l-Arg can accurately release from the nanoparticles. Under further 660 nm laser irradiation, the released Ce6 will produce plenty of singlet oxygen (¹O₂) for PDT, while the generated ¹O₂ can oxidize l-Arg to release NO for the synergy of PDT and gas therapy. The “Linkage Mechanism” can achieve precise release of the payloads under the control of photothermal effect at tumor site, and the chain reaction of PDT and gas therapy overcomes the problem of premature release of gas during transportation. Benefiting from the guidance of fluorescence imaging and second near infrared photoacoustic imaging by Ce6 and CuS, both in vitro and in vivo experiments present effective antitumor efficiencies. The nanoparticles provide new ideas for controllable release of drugs and the synergistic effect of multiple treatments, possessing great application prospects.