AIE-Active Photosensitizers: Manipulation of Reactive Oxygen Species Generation and Applications in Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) is a non-invasive approach for tumor elimination that is attracting more and more attention due to the advantages of minimal side effects and high precision. In typical PDT, reactive oxygen species (ROS) generated from photosensitizers play the pivotal role, determining the efficiency of PDT. However, applications of traditional PDT were usually limited by the aggregation-caused quenching (ACQ) effect of the photosensitizers employed. Fortunately, photosensitizers with aggregation-induced emission (AIE-active photosensitizers) have been developed with biocompatibility, effective ROS generation, and superior absorption, bringing about great interest for applications in oncotherapy. In this review, we review the development of AIE-active photosensitizers and describe molecule and aggregation strategies for manipulating photosensitization. For the molecule strategy, we describe the approaches utilized for tuning ROS generation by attaching heavy atoms, constructing a donor-acceptor effect, introducing ionization, and modifying with activatable moieties. The aggregation strategy to boost ROS generation is reviewed for the first time, including consideration of the aggregation of photosensitizers, polymerization, and aggregation microenvironment manipulation. Moreover, based on AIE-active photosensitizers, the cutting-edge applications of PDT with NIR irradiated therapy, activatable therapy, hypoxic therapy, and synergistic treatment are also outlined.

Nanomaterials as carriers to improve the photodynamic antibacterial therapy

“…There are two main types of photochemical mechanisms of PDAT (Figure 1), including type I reactions and type II reactions (Gupta et al, 2021;Lin et al, 2021;George et al, 2022). Among them, the type I reaction means that after the photosensitizer enters the bacteria, under the irradiation of light of a certain wavelength, the photosensitizer that absorbs photon energy transitions from the ground state S0 to the excited state S1, in which part of the energy is radiated in the form of fluorescent quantum, and the remaining energy will be photosensitive (Winifred Nompumelelo Simelane and Abrahamse, 2021;Donzello et al, 2022;Yu et al, 2022). The agent molecules lead to the excited state T1, which is also called intersystem crossing.…”

Pyrene-Based AIE Active Materials for Bioimaging and Theranostics Applications

“…Likewise, a few sensory reports on pyrene-based derivatives did not address the AIE of the molecules [ 58 ]. Upon the conjugation of pyrene with dye molecules and peptides, the feasible in vivo/in vitro aggregation of those molecules can be applied in bioimaging and theranostic studies [ 62 , 63 , 64 ].…”

Aggregation-Induced Ignition of Near-Infrared Phosphorescence of Non-Symmetric [Pt(C^N*N’^C’)] Complex in Poly(caprolactone)-based Block Copolymer Micelles: Evaluating the Alternative Design of Near-Infrared Oxygen Biosensors

“…Z. Tang’s group in 2001 [ 1 ], various aggregation-induced [ 2 , 3 , 4 ] or aggregation-enhanced [ 5 ] photophysical phenomena have been described. Such an intense focus on AIE and related phenomena stems from realizing the potential benefits of implementing AIE-based emitters (AIEgens) in applications utilizing high emitter concentrations, such as OLED technology [ 1 ], organelle-specific imaging and sensing [ 6 ], as well as photodynamic therapy [ 7 ]. The major advantage of these emitters is that contrary to conventional emitters that quench upon concentrating, AIEgens ignite or enhance their luminescence, two-photon emission, singlet oxygen production, etc.…”

“…In view of the possible practical applications of organometallic AIEgenes as oxygen biosensors, their dispersion stability and compact packing are of significant importance. Generally, AIE can be spatially restricted to small (down to nanometer scale) volumes, which seems to be quite useful in numerous applications [ 7 ]. In particular, such a nano-confinement of AIE provides the possibility for the controlled design of nanoparticle-based oxygen biosensors, as was reported recently for the sensor prototype based on symmetrical [Pt(C^N*N^C)] complexes embedded into aminated polystyrene nanoparticles that demonstrated aggregation-enhanced dual emission in the green and deep red areas of the visible spectrum [ 5 ].…”