Strong π-π Stacking Stabilized Nanophotosensitizers: Improving Tumor Retention for Enhanced Therapy for Large Tumors in Mice

Conventional photosensitizers (PSs) often show poor tumor retention and are rapidly cleared from the bloodstream, which is one of the key hindrances to guarantee precise and efficient photodynamic therapy (PDT) in vivo. In this work, a photosensitizer assembly nanosystem that sharply enhances tumor retention up to approximate to 10 days is present. The PSs are synthesized by meso-substituting anthracene onto a BODIPY scaffold (AN-BDP), which then self-assembles into stable nanoparticles (AN-BDP NPs) with amphiphilic block copolymers due to the strong intermolecular pi-pi interaction of the anthracene. Additionally, the incorporated anthracene excites the PSs, producing singlet oxygen under red-light irradiation. Although AN-BDP NPs can completely suppress regular test size tumors (approximate to 100 mm(3)) by one-time radiation, only 12% tumor growth inhibition rate is observed in the case of large-size tumors (approximate to 350 mm(3)) under the same conditions. Due to the longtime tumor retention, AN-BDP NPs allow single-dose injection and three-time light treatments, resulting in an inhibition rate over 90%, much more efficient than single-time radiation of conventional clinically used PSs including chlorin-e6 (Ce6) and porphyrin with poor tumor retention. The results reveal the importance of long tumor retention time of PSs for efficient PDT, which can accelerate the clinical development of nanophotosensitizers.

Automated summary

In this study, a photosensitizer assembly nanosystem was developed to enhance tumor retention for efficient photodynamic therapy. The long tumor retention time of the photosensitizer nanoparticles allowed for single-dose injection and multiple light treatments, resulting in a high inhibition rate of over 90% for tumor growth.