Synthesis of Mesoporous Polydopamine-Coated Upconversion Nanoparticles for Dual-Enhanced Photodynamic and Photothermal Cancer Therapy

Background: Photodynamic therapy (PDT) is a common cancer treatment strategy that combines the use of light, a photosensitizer, and oxygen to precisely generate reactive oxygen species (ROS). However, the efficacy of this method is limited by the shallow tissue penetration of the short-wavelength lasers involved, and combination therapy with other treatments such as photothermal therapy (PTT) or radiation therapy requires additional lasers or instruments. A new dual therapy approach using a single laser could minimize the treatment procedure. Methods: :Yb,Nd upconversion nanoparticles (UCNPs) were coated with mesoporous silica (MS) for Ce6-loading and coated with mesoporous polydopamine (MP) as a PTT photosensitizer. The PDT and PTT effects were measured using ROS generation detection and a thermal camera, respectively; in vitro cytotoxicity studies and in vivo antitumor efficacy analysis using tumor xenograft mouse models were performed to confirm the dual effects. Results and Discussion: The PDT-PTT UCNPs were successfully synthesized and emit photoluminescence spectra that can be absorbed by Ce6 to induce the PDT effect. Significant ROS generation was observed from U@MSC@MP NPs following 808 nm laser irradiation for 5 min, which corresponded to intracellular ROS detection in human colorectal adenocarcinoma HT-29 cells. The NPs significantly reduced HT-29 cell viability compared with PDT or PTT alone, demonstrating the potential of the designed UCNPs. Moreover, the in vivo antitumor efficacy analysis confirmed the dual effect with no signs of toxicity, supporting the safety and biocompatibility of the synthesized NPs. Conclusion: These findings suggest that the combination of PDT and PTT using a single laser can be achieved with UCNPs. This approach is a promising strategy for simplifying the cancer treatment procedures in clinical applications.