Construction of a nanotheranostic system Zr-MOF@PPa/AF@PEG for improved photodynamic therapy effects based on the PDT‑oxygen consumption and hypoxia sensitive chemotherapeutic drug.

Photodynamic therapy (PDT) has gained much attention in tumor therapy because of its special advantages. PDT heavily depends on the oxygen, yet the tumor microenvironment (TME) is a hypoxic and acid milieu, which weakens the PDT effect. Based on the consideration that the TME deteriorated by the PDT oxygen consumption could activate the hypoxic-sensitive small-molecule drug, we designed and prepared an integrated nanocomposite including zirconium ion metal organic framework (carrier), pyropheophorbide-a (PPa, photosensitizer), and 6-amino flavone (AF, hypoxic-sensitive drug), aiming to exert a cascaded PDT-chemotherapy (CT) antitumor effect and to solve the hypoxic challenge. The prepared nanocomposite showed great stability under the physiological (pH 7.4) condition and could continuously release PPa and AF under slightly acidic pH condition (pH 6.4), suggesting a tumor microenvironment responsive feature. Systematical in vitro and in vivo researches under various conditions (light, dark, hypoxic and normoxic) have showed that the obtained Zr-MOF@PPa/AF@PEG nanoparticles (NPs) had good biocompatibility and could achieve efficient antitumor effects based on PDT- chemotherapy (CT) cascade process. Finally, bright red fluorescence was observed in the tumor cells after internalization implying an application potential in tumor imaging.