Lipid Droplet‐Targetable Fluorescence Guided Photodynamic Therapy of Cancer Cells with an Activatable AIE‐Active Fluorescent Probe for Hydrogen Peroxide

Abstract

remarkable advantages of early diagnosis, visible drug delivery, and therapeutic efficiency, in view of its noninvasive, fast responsive, and highly sensitive properties. [2] In recent years, photodynamic therapy (PDT), which employs a photosensitizer upon light irradiation to bring about cytotoxic reactive oxygen species (ROS), has emerged as a noninvasive and reliable cancer therapeutic modality. Thanks to the inherent fluorescence of photosensitizers, PDT affords a fascinating prospect for fluorescence guided cancer therapy. [3] However, traditional photosensitizers in fluorescence guided PDT (FL-PDT) like porphyrins and phthalocyanines are π-conjugated hydrophobic molecules and strongly aggregate in biological samples. They suffered from aggregation-caused quenching (ACQ) effect due to the intermolecular π−π stacking. [4] The aggregation of photosensitzers, especially after they accumulated in cells, cause severe quenching of both fluorescence and the ROS generation capability, which resulted in poor imaging quality and therapeutic efficiency. [5] Worse more, these "always on" photosensitizers are also emissive in nontumor region, resulting in poor signalto-noise ratio. Thus, it is highly desirable but still very challenging to develop activatable "turn on" photosensitizers with both bright luminescence and high ROS production capability even in the aggregated state for efficient FL-PDT. Fluorescence guided photodynamic therapy (FL-PDT) offers the great opportunity for realizing personalized medicine in the treatment of cancer. Aggregation-induced emission luminogens (AIEgens) with efficient emission and reactive oxygen species (ROS) generation even in the aggregated state are the ideal FL-PDT photosensitizers to overcome the quenched fluorescence and ROS that traditional photosensitizers faced in PDT. Moreover, considering the higher levels of H 2 O 2 in cancer cells than in normal cells and the fact that lipid droplet (LD) accumulation correlates to the enhanced survival rate of cancer cells in hypoxic conditions, it will be very interesting and rewarding to develop a LD-targeted, H 2 O 2 activatable AIE-active photosensitizer for FL-PDT. Thereafter, a LD-targeted fluorescent probe TPECNPB is fabricated for H 2 O 2-activatable fluorescence guided PDT of cancer cells. AIE-active TPECNPB exhibits the unique features of large Stokes shift (175 nm), superior photostability, and excellent selectivity toward H 2 O 2. TPECNPB is able to selectively accumulate in LD and is activated by endogenous H 2 O 2 for light-up bioimaging in live MCF-7 cells. In addition, H 2 O 2-activatable singlet oxygen generation and PDT of cancer cells has also been successfully implemented with TPECNPB. These prominent parameters would make TPECNPB a powerful toolbox for H 2 O 2-activatable and LD-targetable fluorescence guided PDT of cancer cells.

The application of photodynamic inactivation to microorganisms in food

“…It works on the principle that PSs can be activated in certain wavelengths to produce reactive oxygen species (ROS) with strong oxidation, so as to inactivate malignant cells and pathogenic microorganisms ( Jiang et al, 2014 ). The advantages of PDI are that it does not produce toxic chemicals, the only energy required is the light source and the possibility of causing microbial resistance is low due to its multi-target nature ( Costa et al, 2011 ), hence it has been widely applied in the fields of medicine ( Jiang et al, 2020 ), dentistry ( Rocha et al, 2020 ) and environment ( Luksiene & Brovko, 2013 ). Since the beginning of the 21st century, researchers have begun to explore the possibility of using PDI as a novel strategy for food decontamination in a non-thermal way to achieve food safety.…”

Activity‐based smart AIEgens for detection, bioimaging, and therapeutics: Recent progress and outlook

“…To overcome the dilemma of fluorescence quenching and ROS F I G U R E 6 Chemical structures of probes for ROS weakening caused by aggregation of traditional photosensitizers, Wang and coworkers fabricated a H 2 O 2 -activatable AIE-active photosensitizer 45 for fluorescence-guided photodynamic therapy. [127] After molecule 45 was activated by H 2 O 2 overexpressed in cancer cells, the product accumulated in lipid droplets with bright AIE fluorescence and high 1 O 2 generation under light irradiation. In addition, the probe exhibited prominent features including good photostability, a large Stokes shift, and high sensitivity.…”

Three birds with one stone: a single AIEgen for dual-organelle imaging, cell viability evaluation and photodynamic cancer cell ablation

“…35 In addition, recent evidence demonstrated that some AIEgens could also generate reactive oxygen species (ROS) in the aggregation state upon light irradiation, making them effective photosensitizers for photodynamic therapy (PDT). [36][37][38][39][40] For instance, Tang et al rationally constructed a H 2 O 2 -responsive AIE probe TTPy-H 2 O 2 for imaging-guided organelle targeting and photodynamic cancer cell ablation. 38 Wang et al reported a LD-targeted and AIE-active photosensitizer TPECNPB for H 2 O 2 -activatable fluorescence-guided PDT on cancer cells.…”

“…38 Wang et al reported a LD-targeted and AIE-active photosensitizer TPECNPB for H 2 O 2 -activatable fluorescence-guided PDT on cancer cells. 39 Zhao et al developed an esterase-responsive prodrug (TPEQC) by conjugating an anticancer drug of chlorambucil with an AIE active photosensitizer for lysosome/mitochondria dual-targeted and image-guided cancer therapy through synergetic chemo-photodynamic cancer therapy. 40 However, a single AIEgen that is capable of the dual-imaging of mitochondria/lipid droplets, detection of cell viability and simultaneously PDT on cancer cells has rarely been reported.…”