It is very meaningful to develop bifunctional therapeutic agents which can monitor the tumor hypoxia in real time as well as maintain good photodynamic therapy (PDT) effect under hypoxia. To achieve it, herein, a series of hydrophilic phosphorescent starburst Pt(II) porphyrins as bifunctional therapeutic agents for simultaneous tumor hypoxia imaging and highly efficient PDT have been rationally designed and synthesized. They have been obtained by using Pt(II) porphyrins as the functional core and cationic oligofluorenes as the arms. Such a three-dimensional structural feature ensures their hydrophilicity, ultrasensitive oxygen-sensing performance, and high 1O2 quantum yields. Furthermore, the O2-sensitive phosphorescence lifetimes of starburst Pt(II) porphyrins are beneficial to eliminate the interference from background fluorescence remarkably and enhance the signal-to-noise ratio of hypoxia imaging by using phosphorescence lifetime imaging microscopy. Their PDT effects were also evaluated both in vitro (under both hypoxia and normoxia) and in vivo. As a result, tumor hypoxia can be significantly differentiated and tumor growth can be inhibited effectively, while the systemic toxicity is not observed. All of these results demonstrate that starburst Pt(II) porphyrins could be used as the promising bifunctional therapeutic agents for early diagnosis and treatment of cancer.
Keywords: hypoxia imaging; photodynamic therapy; starburst Pt(II) porphyrins; therapeutic agents; tumor.