Reducing photosensitizer aggregation via cyclodextrin–adamantane porphyrin host–guest interactions for enhanced photodynamic therapy

Abstract

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 Cu2−xSe-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 Cu2−xSe-CD-TPP. In this construct each photosensitizer molecule is individually confined within the cavity of a cyclodextrin unit anchored on the surface of Cu2−xSe 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 Cu2−xSe-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.