Integrating Pillar[5]arene and BODIPY for a Supramolecular Nanoplatform To Achieve Synergistic Photodynamic Therapy and Chemotherapy

Abstract BODIPY photosensitizers have been integrated with a hypoxia‐activated prodrug to achieve synergistic photodynamic therapy (PDT) and chemotherapy. A novel BODIPY derivative BDP‐CN was designed and synthesized. It had two cyano groups to make it complex well with a water‐soluble pillar[5]arene. Their association constant was calculated to be (6.8±0.9)×106 M−1. After self‐assembly in water, regular spherical nanocarriers can be formed; these were used to encapsulate the hypoxia‐activated prodrug tirapazamine (TPZ). BDP‐CN displayed excellent photodynamic activity to complete PDT. In this process, O2 can be continuously consumed to activate TPZ to allow it to be converted to a benzotriazinyl (BTZ) radical with high cytotoxicity to complete chemotherapy. As a result, the formed nanoparticles showed excellent synergistic photodynamic therapy and chemotherapy efficacy. The synergistic therapy mechanism is discussed in detail.