A potent mannose-modified pillararene-BODIPY system for photodynamic therapy

Photodynamic therapy (PDT) offers a promising, non-invasive approach to cancer treatment. However, its efficacy is often limited by the poor water solubility, low cellular uptake, and high dose requirements of traditional photosensitizers, which can lead to side effects like skin photosensitivity. This study presents a novel supramolecular photosensitizer, PS3⊂WP5, comprising a mannosylated pillar[5]arene (WP5) host and a near-infrared BODIPY photosensitizer (PS3). This host-guest complex exhibits a strong binding affinity (<i>K</i>_a = 5.10 × 10⁶ M^-1) and self-assembles into nanoparticles in water. PS3⊂WP5 demonstrates high singlet oxygen quantum yield (<i>Φ</i>_Δ = 0.95) upon irradiation at 633 nm, along with excellent photostability. <i>In vitro</i> experiments confirm that PS3⊂WP5 exhibits superior PDT efficacy, good biocompatibility, and low dark toxicity compared to the free PS3, which suffers from poor aqueous solubility, low stability, and limited cellular uptake. This supramolecular approach offers a promising strategy for the design of multifunctional nanomaterials for cancer phototherapy, potentially overcoming the limitations of conventional photosensitizers and paving the way for the development of more efficient PDT agents with enhanced clinical potential.