Supramolecular Aggregation-Induced Emission Photosensitizer Encapsulated by Cucurbit[8]uril Nanocavity Boosts Hypoxia-Activated Tumor Therapy
Wen Liu, Zeyu Zhang, Qing Huang, Reet Pai, Lucas Liu, Zufeng Ding, Xing Wang, Zhicheng Jin
Abstract
High Resolution Image Download MS PowerPoint Slide The limited efficacy of chemotherapy induced by the hypoxic tumor microenvironment remains a major obstacle in clinical oncology. To address this, we designed and synthesized a series of aggregation-induced emission photosensitizers with donor−π–acceptor structures, exemplified by SC-3. Upon assembly with cucurbit[8]uril (CB[8]), the nanosupramolecular photosensitizer 2SC-3/CB[8] significantly enhanced singlet oxygen ( 1 O 2 ) generation and exacerbated cellular hypoxia. When coadministered with the hypoxia-activated chemotherapeutic tirapazamine (TPZ), we found that 2SC-3/CB[8] further amplified TPZ’s antitumor efficacy in MDA-MB-231 breast cancer cells. Experimental studies and density functional theory calculations confirmed that SC-3 exhibits potent photodynamic therapy activity with high mitochondrial specificity. In addition, we found that CB[8]-induced depletion of intracellular spermine further contributed to the death of the tumor cells. Together, these findings highlight the potential of combining supramolecular photosensitizers with hypoxia-activated chemotherapy as a promising and synergistic strategy for the treatment of solid tumors.