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.