Radical induced quartet photosensitizers with high 1O2 production for in vivo cancer photodynamic therapy

Abstract

Singlet oxygen (1O2) is a strong oxidant which plays important roles in photodynamic therapy (PDT). The exploitation of photosensitizers with high 1O2 production is crucial to improve PDT efficiency. In this study, a radical labeled quartet photosensitizer Cy-DENT is reported with high singlet oxygen quantum yield (ΦΔ=32.3%) due to a radical enhanced inter-system crossing (ISC) process. After the introduction of 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) radical, quartet state 4[R,T] of Cy-DENT could be formed to give an over 20-fold enhancement of singlet oxygen quantum yield compared to Cy-DEN (without TEMPO radical) under irradiation of near infrared (NIR) light. In addition, the 1O2 production is well controlled by varying the electron-donating ability of the terminal substituent group. Cy-DENT possesses good cell permeability and is localized in mitochondria. Under the irradiation of 700 nm light, Cy-DENT can produce high levels of ROS to destroy the mitochondria membrane potential and induce cell apoptosis. Through the encapsulation of PEG-SS-PCL micelle, Cy-DENT can be effectively delivered to tumors and suppresses the tumor growth after PDT treatment.