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-1α 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 H(2)O(2) 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-1α 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.