Enhancing the Photosensitivity of Hypocrellin A by Perylene Diimide Metallacage-Based Host–Guest Complexation for Photodynamic Therapy

Highlights A new type of metallacage was successfully fabricated and used as containers for hypocrellin-type photosensitizers, which prevented the self-aggregation of photosensitizers in aqueous solution. The metallacage was also employed as an energy donor to promote the singlet oxygen generation ability via fluorescence resonance energy transfer, thereby achieving highly efficient photodynamic therapy. The development of supramolecular hosts which can efficiently encapsulate photosensitizers to improve the photodynamic efficacy holds great promise for cancer therapy. Here, we report two perylene diimide-based metallacages that can form stable host–guest complexes with planar conjugated molecules including polycyclic aromatic hydrocarbons and photosensitizers (hypocrellin A). Such host–guest complexation not only prevents the aggregation of photosensitizers in aqueous environments, but also offers fluorescence resonance energy transfer (FRET) from the metallacage to the photosensitizers to further improve the singlet oxygen generation (Φ Δ = 0.66). The complexes are further assembled with amphiphilic polymers, forming nanoparticles with improved stability for anticancer study. Both in vitro and in vivo studies indicate that the nanoparticles display excellent anticancer activities upon light irradiation, showing great potential for cancer photodynamic therapy. This study provides a straightforward and effective approach for enhancing the photosensitivity of conventional photosensitizers via host–guest complexation-based FRET, which will open a new avenue for host–guest chemistry-based supramolecular theranostics.