Hemicyanine-Based Type I Photosensitizers for Antihypoxic Activatable Photodynamic Therapy

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 fluorophotoacoustic 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.

Recent Advances in Photosensitizer Materials for Light‐Mediated Tumor Therapy

“…For example, Zhang et al modified hemicyanine by Br atoms (CyBr) to increase the SOC, leading to more efficient ISC to expand the lifetime of triplet state exciton. [44] They further modified CyBr by phosphorylation to achieve an activatable probe (CyBrP) that can specifically unlock its fluoro-photoacoustic signals and phototoxicity upon interaction with alkaline phosphatase, an enzyme overexpressed in tumors. Similarly, Hu et al systematically examined halogenated boron dipyrromethene (BODIPY) photosensitizers.…”

Tumor Microenvironment Activatable Nanoprodrug System for In Situ Fluorescence Imaging and Therapy of Liver Cancer

“…In comparison with other imaging analytical methods, near-infrared (NIR) fluorescence imaging is widely applied in the study of biosystems because of its distinct merits such as low cost, high sensitivity, and noninvasive. − Especially, small molecule probes based on organic dyes, with lower toxicity and easy metabolism, have become robust tools for the observation of various bioanalytes. − Up to now, diverse small molecule fluorescent probes have been prepared to detect pH, ROS, enzymes, etc. in tumor cells. − Nevertheless, the majority of reported probes were at risk of diffusion owing to the lack of in situ labeling capability, leading to spurious signals, and were not appropriate for tracking in the long term. Moreover, they could also result in signal deficiencies in bioimaging, thus giving unreliable measurements.…”

Rational design of type-I photosensitizer molecules for mitochondrion-targeted photodynamic therapy

“…Type-I PSs with low oxygen dependence offer new approaches for PDT. 11 Although several strategies, including donor–acceptor systems, electron-rich anion-π + incorporation, polymerization and cationization, have been developed to prepare type-I PSs, 12–25 the design of type-I PSs remains a challenge. The conversion of an excited type-II PS into a type-I PS by easy modification is a good alternative approach for constructing new type-I PSs.…”