Reducing photosensitizer aggregation via cyclodextrin-adamantane porphyrin host-guest interactions for enhanced...

The production yield of singlet oxygen (¹O₂) directly determines the therapeutic efficacy of photodynamic therapy (PDT). However, photosensitizer aggregation seriously suppresses ¹O₂ production. Herein, we developed a host-guest complexation-based isolation strategy that prevents photosensitizers' aggregation, enhances ¹O₂ generation and ultimately boosts the photodynamic killing performance. Specifically, we synthesized ultra-small Cu_2-x Se-CD nanoparticles as a supramolecular loading platform and loaded them with adamantane-functionalized 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (Ada-TPP) to obtain a supramolecular nano-photosensitizer Cu_2-x Se-CD-TPP. In this construct each photosensitizer molecule is individually confined within the cavity of a cyclodextrin unit anchored on the surface of Cu_2-x Se nanoparticles, endowing the material with excellent dispersibility and effectively suppressing the photosensitizer's aggregation. This rational structural design results in an 84.8% increase in ¹O₂ production yield. Both in vitro and in vivo experiments confirm that Cu_2-x Se-CD-TPP achieves efficient tumor therapy under light irradiation. Collectively, this study not only provides a robust strategy to mitigate photosensitizers' aggregation, but also develops a promising nanomaterial for precise and high-efficacy photodynamic therapy.