Combined Prussian Blue Nanozyme Carriers Improve Photodynamic Therapy and Effective Interruption of Tumor Metastasis

Introduction: Photodynamic therapy (PDT) as a new technique for theranostics is to kill tumor cells by activating photosensitizer and interacting with oxygen (O-2) to produce reactive oxygen species (ROS). However, the hypoxic tumor microenvironment (TME) may constrain the efficacy of PDT. Moreover, the lack of O-2 in TME also up-regulates the expression of HIF-la and promotes tumor metastasis, which is also a leading cause of death for terminal cancer patients. Methods: Prussian blue (PBs) was firstly synthesized by hydrothermal method, which was then etched by hydrochloric acid to obtained hollow Prussian blue nanoparticles (HPBs). Afterwards, Au-Pt nanozymes were in situ growing on the HPBs by reduction method to prepare Au-Pt@HPBs (APHPBs). Owing to the hollow structure of APHPBs, photosensitizer Ce6 can be easily and efficiently loaded into it to obtain Ce6-Au-Pt@HPBs (Ce6-APHPBs). After ce6-APHPBS regulation, photoacoustic imaging and hypoxic fluorescence imaging were then used to evaluate changes in hypoxic TME in vivo. Finally, under the assistant of Ce6-APHPBs, we evaluated the inhibitory effect of enhanced PDT on primary and metastatic tumors. Results: We first designed and synthesized Ce6 loaded hollow prussian blue nanoparticles with Au-Pt nanozymes grown in situ on it. Both in vitro and in vivo experiments show that the prepared Ce6-APHPBs have good biosafety and could effectively degrade the overexpressed H2O2 in TME to generate O-2, further relieve the hypoxic TME and thus enhance the effect of PDT. At the same time, the increasing O-2 content could also reduce the expression of HIF-1 alpha at the tumor site, which could reduce lung metastasis. Conclusion: Ce6-APHPBs designed by us could not only efficiently enhance PDT but also regulate TME to reduce tumor metastasis and prolong survival of mice, which provide a novel idea and strategy for clinical PDT and metastatic tumor.