A Highly Water‐Soluble Aggregation‐Induced Emission Luminogen with Anion‐π⁺ Interactions for Targeted NIR Imaging of Cancer Cells and Type I Photodynamic Therapy

Abstract

The low oxygen dependence of type I photosensitizers (PSs) has made them a popular choice for treating solid tumors. However, the drawbacks of poor water solubility, short emission wavelength, poor stability, and inability to distinguish cancer cells from normal cells limit the application of most type I PSs in clinical therapy. Thereby, developing novel type I PSs for overcoming these problems is an urgent but challenging task. Herein, by utilizing the distinctive structural characteristics of anion‐π+ interactions, a highly water‐soluble type I PS (DPBC‐Br) with aggregation‐induced emission (AIE) characteristic and near‐infrared (NIR) emission is fabricated for the first time. DPBC‐Br displays remarkable water solubility (7.3 mM) and outstanding photobleaching resistance, enabling efficient and precise differentiation between tumor cells and normal cells in a wash‐free and long‐term tracking manner via NIR‐I imaging. Additionally, the superior type I reactive oxygen species (ROS) produced by DPBC‐Br provide both specific killing of cancer cells in vitro and inhibition of tumor growth in vivo, with negligible systemic toxicity. This study rationally constructs a highly water‐soluble type I PS, which has higher reliability and controllability compared with conventional nanoparticle formulating procedures, offering great potential for clinical cancer treatment.

In situ fluorescence visualizing of a temperature-dependent photoreaction process of pyridazine N-oxide

“…1C show that the PL intensity of MPD-O decreased slowly with the water fraction to lower than 80%, attributable to the twisted intramolecular charge transfer (TICT) effect. 40,41 When the f w continued to increase from 80% to 99%, the PL intensity was enhanced dramatically due to the twisted conformation of the triphenylamine group resulting in the restriction of intramolecular motions (RIM) in the aggregated state, 42 indicating the typical AIE feature of MPD-O. To facilitate an in-depth understanding of the AIE features of MPD-O, the single crystal analysis was carried out.…”

Multifunctional Self-Assembled Nanoplatform with AIEgen and Rapamycin-Mediated Tumor Microenvironment Remodeling via mTOR Axis to Enhance Photodynamic Therapy

“…9,25 It is inevitable to lose one or the other through amphiphilic carrier delivery or hydrophilic polymer modification of AIEgens, which will bring problems such as short emission wavelength, weak ROS generation, and complex purification procedures. 25 A groundbreaking work has constructed carrier-free multifunctional self-assembled nanoplatforms containing AIEgen-TNTP and Ra to simultaneously overcome ACQ, hypoxia, and immunosuppressive TME (Scheme 1). The newly synthesized zwitterionic AIEgen-TNTP can self-assemble into spherical nanoparticles (TNTP NPs) in water by a simple preparation method and further load the water-insoluble anticancer drug Ra via hydrophobic interaction to form multifunctional self-assembled nanoplatforms (TNTP-Ra NPs).…”

“…Currently, most of the developed PS are type II, which essentially rely on O 2 to produce ROS, so the ubiquitous hypoxic microenvironment of solid tumors limits the application. , Compared with type II PS, type I PS has less dependence on O 2 and more potent cytotoxicity of free radical ROS. , Therefore, exploring type I AIEgens with high-performance ROS production is necessary to enhance the PDT efficacy. Despite this, the development of AIEgens with type I ROS production capacity is still in its infancy and requires further research and great efforts. , …”

“…28 Currently, an increasing AIEgens developed for type I PDT has become a research hotspot, but its hydrophobic large conjugate structure is still a significant obstacle to practical application. 9,25 It is inevitable to lose one or the other through amphiphilic carrier delivery or hydrophilic polymer modification of AIEgens, which will bring problems such as short emission wavelength, weak ROS generation, and complex purification procedures. 25 A groundbreaking work has constructed carrier-free multifunctional self-assembled nanoplatforms containing AIEgen-TNTP and Ra to simultaneously overcome ACQ, hypoxia, and immunosuppressive TME (Scheme 1).…”

Recent advances in aggregation‐induced emission–active type I photosensitizers with near‐infrared fluorescence: From materials design to therapeutic platform fabrication

“…PDT outcome in vivo was also evaluated, and the tumor growth could be well suppressed after white light irradiation (Figure 8f). This work developed a highly water‐soluble type I PS with NIR emission, wash‐free targeted bioimaging to lysosome and mitochondria, and great PDT outcome, offering great potential for clinical cancer treatment [70].…”