Highly Efficient Multifunctional Organic Photosensitizer with Aggregation-Induced Emission for In Vivo Bioimaging and Photodynamic Therapy

Abstract

Photosensitizers play a critical role in photodynamic therapy (PDT). Multifunctional organic nanoparticles (NPs) that possess bright fluorescence in aggregates, high singlet oxygen (1O2) quantum yield, near-infrared (NIR) absorption and emission, large Stokes shift, two-photon bioimaging, specific organelle targeting, high PDT efficiency, as well as good biocompatibility and photostability are ideal candidate photosensitizers for image-guided PDT. Due to its enhanced fluorescence and high 1O2 generation efficiency in aggregate states, photosensitizers with aggregation-induced emission (AIE) characteristics have attracted increasing interest in PDT. In this study, a new AIE-active Schiff base 5-(((5-(7-(4-(diphenylamino)­phenyl)­benzo­[c]­[1,2,5]­thiadiazol-4-yl)­thiophen-2-yl)­methylene)­amino)-3-methylthiophene-2,4-dicarbonitrile (TBTDC) based on a D–A−π–A skeleton has been designed and synthesized, and it can be readily encapsulated by Pluronic F-127 to form uniform nanoparticles. TBTDC NPs exhibit bright NIR emission at 825 nm with a Stokes shift up to 300 nm, impressive two-photon bioimaging capability with tissue penetration deep into 300 μm, high 1O2 generation quantum yield (0.552), specific targeting to lysosome, as well as good biocompatibility and photostability. Furthermore, TBTDC NPs present remarkable cytotoxicity for tumor cells and suppression of tumor growth in nude mice through reactive oxygen species generation upon white light irradiation. These results reveal that TBTDC NPs have great potential to become excellent candidates for multifunctional organic photosensitizers for two-photon bioimaging and image-guided PDT and are promising in future clinical applications.

Multiple Light-Activated Photodynamic Therapy of Tetraphenylethylene Derivative with AIE Characteristics for Hepatocellular Carcinoma via Dual-Organelles Targeting

“…Recently, some AIEgens were designed to exhibit excellent photosensitization and ROS generation ability, which broadens their potential applications in PDT of cancer. The unique features of AIEgens provide new opportunities for the facile design of PS with special function, high accuracy, and efficacy for image-guided PDT [30][31][32][33].…”

Aggregation-induced emission photosensitizer-based photodynamic therapy in cancer: from chemical to clinical

“…In addition, nanoparticles formed by AIE-PSs contribute to PDT for breast cancer. Liu et al encapsulated a single AIE-PS into F-127 to form nanoparticles (TBTDC NPs), which exhibited good biocompatibility, highly specific targeting of lysosomes, and impressive tissue penetration (up to 300 μm) [ 194 ]. Cell viability of MCF-7 cells incubated with TBTDC NPs was detected via CCK-8 assay.…”

Photosensitizer Encryption with Aggregation Enhanced Singlet Oxygen Production

“…A significant current disadvantage in the implementation of photosensitizers based on conjugated chromophore molecules is their tendency to aggregate in aqueous media because of either general insolubility or enhancement of hydrophobic intermolecular interactions . Aggregation typically causes deactivation of photosensitizers in vivo even if excellent 1 O 2 generation properties are found in vitro . − To ameliorate for aggregation-induced effects, various nanoarchitecturing strategies, as well as numerous macroscale architectures, ,− have been proposed for the sequestration of the photosensitizer moiety to suppress deactivation. , These nanoscale architectures include the encapsulation of photosensitizers in lipid particles or colloids, , incorporation into dendrimeric , or polymeric , architectures, or inclusion of the photosensitizers in hybrid core–shell nanoparticles − or porous nanomaterials. − Multifunctional self-assembled nanostructures have also been investigated although these approaches have often involved highly technical multistep syntheses leading to complex nanosystems of limited stability or efficacy. , Conversely, compared to aggregation-induced/enhanced emission (AIEE), aggregation-induced/enhanced 1 O 2 generation by photosensitizers has hardly been demonstrated for PDT applications. − That being said, there have been several recently reported examples utilizing AIEE photosensitizers in vitro and in vivo ; , however, despite the utilization of AIEE agents, surfactants to stabilize and/or ensure biocompatibility are still required in some cases. − …”