Self-Reporting Hypoxia-Responsive Supramolecular Phototheranostic Nanomaterials Based on AIEgen and Azocalixarene

Hypoxia is a significant feature in most of solid tumors and developing hypoxia-responsive phototheranostic system is still a challenge. In this contribution, a supramolecular assembly strategy based on sulfonate-functionalized azocalix[4]arene (SAC4A) and cationic aggregation-induced emission photosensitizer (namely TPA-H) was proposed for hypoxia-responsive bioimaging and photodynamic therapy (PDT). Upon supramolecular complexation of TPA-H and SAC4A through electrostatic interaction, the fluorescence and reactive oxygen species (ROS) generation of TPA-H were largely inhibited. In hypoxic tumors, the azo group of SAC4A can be reduced to aniline derivative and release the included TPA-H to recover its pristine fluorescence and ROS. Interestingly, the free TPA-H undergoes cell membrane-to-mitochondria translocation during cell imaging, achieving a real-time self-reporting PDT system. In vivo tumor imaging and therapy reveal that this as-prepared supramolecular complexes have good biosafety and efficient antitumor activity under hypoxia. Such hypoxia-responsive supramolecular photosensitizer system will enrich image-guided PDT.