Recent advances in photodynamic therapy systems based on pillar[n]arene host-guest chemistry.

Photodynamic therapy (PDT) is a minimally invasive and low-toxicity strategy for tumors and bacterial infections. However, conventional small-molecule photosensitizers have poor water solubility, severe aggregation-caused quenching and weak tumor targeting, restricting their clinical translation. Macrocyclic host-guest supramolecular assembly improves the performance of photosensitizers via reversible noncovalent recognition. Pillar[n]arenes feature symmetric electron-rich cavities, abundant modifiable sites and wide guest compatibility, showing outstanding advantages over cyclodextrins, calixarenes and cucurbiturils for responsive photosensitizing platforms. This review summarizes recent advances of pillar[n]arene host-guest systems in PDT. We introduce the structural and recognition features of pillar[n]arenes, classify the fabrication of pillar[n]arene-photosensitizer complexes, and interpret how host-guest inclusion alleviates fluorescence quenching, elevates singlet oxygen yield and triggers tumor microenvironment-responsive drug release. Their applications in anti-tumor PDT, antibacterial photodynamic disinfection and imaging-guided therapy are outlined. We also discuss translational obstacles including insufficient biocompatibility and limited deep-tissue penetration, and propose future directions involving targeted functionalization, multi-modal synergy and degradable macrocyclic skeletons. This work clarifies the structure-activity relationship of pillar[n]arene-based PDT systems and offers guidelines for designing high-performance supramolecular theranostic agents.