Photodynamic therapy (PDT) and photothermal therapy (PTT) have emerged as promising non-invasive approaches to cancer treatment. However, the development of multifunctional nanomedicines is necessary to enhance these approaches' effectiveness and safety. In this study, we investigated a polydopamine-based nanoparticle (PDA-ZnPc+ Nps) loaded with the efficient photosensitizer ZnPc(4TAP)12+ (ZnPc+) through in vitro and in vivo experiments to achieve synergistic PDT and PTT. Our results demonstrated that PDA-ZnPc+ Nps exhibited remarkable efficacy due to its ability to generate reactive oxygen species (ROS), induce photothermal effects, and promote apoptosis in cancer cells. Moreover, in both MCF-7 cells and MCF-7 tumor-bearing mice, the combined PDT/PTT treatment with PDA-ZnPc+ Nps led to synergistic effects. Subcellular localization analysis revealed a high accumulation of ZnPc+ in the cytoplasm of cancer cells, resulting in cellular disruption and vacuolation following synergistic PDT/PTT. Furthermore, PDA-ZnPc+ Nps exhibited significant antitumor effects without causing evident systemic damage in vivo, enabling the use of lower doses of photosensitizer and ensuring safer treatment. Our study not only highlights the potential of PDA-ZnPc+ Nps as a dual-functional anticancer agent combining PDA and PTT but also offers a strategy for mitigating the side effects associated with clinical photosensitizers, particularly dark toxicity.
Keywords: nanomedicine; photodynamic therapy; photosensitizer; photothermal therapy; synergistic therapy.