H₂O₂-Sensitive Upconversion Nanocluster Bomb for Tri-Mode Imaging-Guided Photodynamic Therapy in Deep Tumor Tissue

Low penetration depth of excited light, undesirable distribution of photosensitizers, severe hypoxia, and inefficient reactive oxygen species (ROS) generation in tumors, lead to the poor therapeutic effects in photodynamic therapy. Herein, a multifunctional nanocluster bomb (UCGM naonoparticles) composed of upconversion nanoparticles (NPs), CeO_x, graphite-C₃N₄ (g-C₃N₄) NPs, and metformin (Met) are developed to mitigate the hypoxia by oxidizing H₂O₂ into O₂ due to the catalysis of CeO_x. The presence of Met can act on the mitochondrion to inhibit the respiration of tumor cells, further improving the O₂ level. Meanwhile, g-C₃N₄ NPs are released from UCGM NPs and penetrate tumor tissue deeply because of their small size. Upon 808 nm laser illumination, UCGM NPs show remarkable photothermal ability and efficiently convert near infrared to ultraviolet light to activate the g-C₃N₄ NPs to generate ROS in a whole tumor to facilitate a combined antitumor effect against deeply located tumors. Moreover, these UCGM NPs also display excellent performances in upconversion luminescence, magnetic resonance imaging, and computerized tomographic imaging, making them a potential imaging-guided drug delivery system in cancer therapy.