Strong π-π Stacking Stabilized Nanophotosensitizers: Improving Tumor Retention for Enhanced Therapy to Large Tumor 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, we present a photosensitizer assembly nanosystem that sharply enhances tumor retention up to ∼10 days. The PSs are synthesized by meso-substituting anthracene onto the BODIPY scaffold (AN-BDP), which then self-assemble into stable nanoparticles (AN-BDP NPs) with amphiphilic block copolymers due to the strong intermolecular π-π interaction of anthracene. Additionally, the incorporated anthracene excites the PSs, producing singlet oxygen under red light irradiation. Although AN-BDP NPs could completely suppress regular test size tumor (∼100 mm3 ) by one-time radiation, only 12% tumour growth inhibition rate was observed in the case of large size tumor (∼350 mm3 ) under the same conditions. Due to the long time tumor retention, AN-BDP NPs allows single-dose injection and three-time light treatments, resulting in an over 90% inhibition rate, much more efficient than single-time radiation of conventional clinically used PSs including chlorin (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. This article is protected by copyright. All rights reserved.