Hemicyanine-Based Type I Photosensitizers for Antihypoxic Activatable Photodynamic Therapy
Yuyang Zhang, Min Zhao, Jia Miao, Wei Gu, Jieli Zhu, Baoliang Cheng, Qing Li, Qingqing Miao
Abstract
Type I photosensitizers provide great potential for effective antihypoxia cancer treatment because of their low O 2 reliance. To achieve tumor specificity, activatable type I photosensitizers that can selectively respond to tumor-related stimuli and thereafter activate their phototoxicity are urgently required, which however are rare. We herein report a hemicyanine-based scaffold with effective type I photoreactions for activatable antihypoxic PDT against tumors. The common hemicyanine (Cy) endows minimized ROS generation, which can be nicely tuned to boost type I ROS production by introducing the halogens to increase the spin–orbit coupling (SOC) constant and thus favor the intersystem crossing (ISC) rate. The optimized CyBr is further modified to achieve an activatable probe (CyBrP) that can specifically unlock its fluoro-photoacoustic signals and phototoxicity upon interaction with alkaline phosphatase (ALP) overexpressed in tumors. By virtue of the high sensitivity and selectivity toward ALP as well as the low O 2 -dependence of type I ROS generation, CyBrP allows for precise phototheranostics of tumors, leading to effectively suppressed tumor growth in living mice. Therefore, this study presents a facile halogen-substituted strategy to construct hemicyanine-based type I photosensitizers that can serve as universal scaffolds for activatable antihypoxia PDT.