Molecular Engineering to Boost AIE‐Active Free Radical Photogenerators and Enable High‐Performance Photodynamic Therapy under Hypoxia

Abstract

The severe hypoxia in solid tumors and the vicious aggregation-caused fluorescence quenching (ACQ) of conventional photosensitizers (PSs) have limited the application of fluorescence imaging-guided photodynamic therapy (PDT), although this therapy has obvious advantages in terms of its precise spatial-temporal control and noninvasive character. PSs featuring type I reactive oxygen species (ROS) based on free radicals and novel aggregationinduced emission (AIE) characteristics (AIE-PSs) could offer valuable opportunities to resolve the above problems, but molecular engineering methods are rare in previous reports. Herein, a strategy is proposed for generating stronger intramolecular charge transfer in electron-rich anion-π + AIE-active luminogens (AIEgens) to help suppress nonradiative internal conversion and to promote radiative and intersystem crossing to boost free radical generation. Systematic and detailed experimental and theoretical calculations prove the proposal herein: the electron-donating abilities are enhanced in collaborative donors, and the AIE-PSs exhibit higher performance in near-infrared fluorescence imaging-guided cancer PDT in vitro/vivo. This work serves as an important reference for the design of AIE-active free radical generators to overcome the ACQ and tumor hypoxia challenges in PDT.

Aggregation-Induced Generation of Reactive Oxygen Species: Mechanism and Photosensitizer Construction

“…In addition to the usage of indicators to detect the type of ROS, the operation of instruments is also completely feasible. As shown in Figure 11 A, EPR spectroscopy was used to provide solid evidence for the free radical ROS generation of four AIE–PSs [ 54 ]. Both BMPO under irradiation and BMPO + AIEgens ( 30 and 31 ) in the dark did not produce any signal in the EPR spectra.…”

Rational design of iridium–porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents

“…[30][31][32][33] Hence, synergistic PDT and PTT treatment is a more effective prospect for tumor therapy in terms of concurrent metastasis than single PDT or PTT. [34][35][36][37][38][39][40] Therefore, achieving long-wavelength excitation of PSs is a very important goal to realize PTT and to effectively overcome the oxygen dependence in PDT, and ultimately to improve the clinical outcome of phototherapy.…”

Mitochondria-anchoring and AIE-active photosensitizer for self-monitored cholangiocarcinoma therapy

“…[14][15][16] In contrast with the traditional PSs, the aggregation-induced emission fluorogens (AIEgens) with rotor structures have significant advantages in terms of high emission efficiency and photodynamic activity in the aggregate state. [17][18][19][20][21][22][23][24][25] Mitochondria are the cell's energy sources, and mitochondriatargeted PSs could greatly improve the efficiency of photodynamic ablation of cancer cells. 26 Recently, mitochondria-targeted and AIE-active PSs with high ROS generation efficiency have shown great potential to kill cancer cells.…”