Enhancing NIR-II Phosphorescence through Phosphorescence Resonance Energy Transfer for Tumor-Hypoxia Imaging

Abstract

Phosphorescence probes have emerged as a promising hypoxia detector for their excellent characters of long luminescence lifetime, large Stokes shift, and oxygen sensitivity. However, the low quantum yields of organic phosphorescence probes in the second near-infrared wavelength window (NIR-II, 1000−1700 nm) hinder their further development of NIR-II hypoxia imaging. Herein, this study reports a new NIR-II phosphorescence probe (PRET NPs) containing a phosphorescent long-lived triplet energy donor (PD) and a NIR-II fluorescent energy acceptor (FA) by using phosphorescence resonance energy transfer (PRET) strategy. Because of the suitable spectral overlap of PD and FA, PRET NPs exhibit high NIR-II quantum yield in both normoxic and oxygen-free atmospheres. Based on that, in the in vivo tumor hypoxia imaging experiments, PRET NPs also exhibit high brightness and signal-to-background ratio (SBR) of NIR-II tumorhypoxia imaging. Therefore, this study illustrates a general approach based on "PRET" strategy to develop bright NIR-II phosphorescent probes.

Brightness Strategies toward NIR-II Emissive Conjugated Materials: Molecular Design, Application, and Future Prospects

“…According to the features of the hypoxic tumor environment, Zhang et al developed a hypoxia-activated tumor diagnostic NIR-II probe via a phosphorescence resonance energy transfer (PRET) strategy that can respond to a hypoxic environment to turn on strong NIR-II fluorescence. 136 The NIR-II probe consisted of a phosphorescent donor and a high-brightness D−A−D NIR-II emissive conjugated material as an acceptor (Figure 12a). As shown in Figure 12b,c, the NIR-II emission intensity of the PRET NPs in a hypoxic environment was more than 2.9 times greater than that in a normoxic environment as a result of improving the accuracy of tumor diagnosis.…”

“…For example, oxygen (O 2 ) is essential for organisms and is not only a requirement for respiration but also a critical gas signaling molecule involved in diverse physiological and pathological processes. According to the features of the hypoxic tumor environment, Zhang et al developed a hypoxia-activated tumor diagnostic NIR-II probe via a phosphorescence resonance energy transfer (PRET) strategy that can respond to a hypoxic environment to turn on strong NIR-II fluorescence . The NIR-II probe consisted of a phosphorescent donor and a high-brightness D–A–D NIR-II emissive conjugated material as an acceptor (Figure a).…”

“…(d) Fluorescence images in the NIR-II region of tumor-bearing mice after administration of PD NPs and PRET NPs at various time points. Reproduced with permission from ref . Copyright 2023, American Chemical Society.…”

Cucurbit[8]uril Confinement-Based Secondary Coassembly for High-Efficiency Phosphorescence Energy Transfer Behavior

“…Supramolecular near-infrared (NIR) emissive materials have aroused significant research interest owing to their outstanding features such as good spatial resolution, deep tissue penetration, and low background noise, which possess promising application values in the fields of biological imaging, − disease theranostics, − organic light-emitting devices, , and biomedical sensors. − Particularly, macrocycle-involved host–guest complexation have been turned out to be a valid strategy to construct NIR luminescent materials especially in aqueous environment. − The guest chromophores are tightly encapsulated into the cavity of well-crafted artificial macrocyclic hosts like cyclodextrins, , cucurbiturils, − and pillararenes , enabled by noncovalent interactions, which can alter molecular conformation and packing modes, thereby ultimately restricting molecular rotation or forming J-aggregates with enhanced red-shifted emissions. Alternatively, Föster resonance energy transfer (FRET)-based supramolecular artificial light-harvesting system is recognized as another feasible protocol to realize long-range NIR luminescence with large Stokes shift at a relatively high donor/acceptor ratio, − which concurrently avoids burdensome covalent chemical synthesis or modification of fluorophores and endows the system with precise controllability.…”

“…Supramolecular near-infrared (NIR) emissive materials have aroused significant research interest owing to their outstanding features such as good spatial resolution, deep tissue penetration, and low background noise, which possess promising application values in the fields of biological imaging, 1 − 4 disease theranostics, 5 − 7 organic light-emitting devices, 8 , 9 and biomedical sensors. 10 − 12 Particularly, macrocycle-involved host–guest complexation have been turned out to be a valid strategy to construct NIR luminescent materials especially in aqueous environment. 13 − 16 The guest chromophores are tightly encapsulated into the cavity of well-crafted artificial macrocyclic hosts like cyclodextrins, 17 , 18 cucurbiturils, 19 − 22 and pillararenes 23 , 24 enabled by noncovalent interactions, which can alter molecular conformation and packing modes, thereby ultimately restricting molecular rotation or forming J-aggregates with enhanced red-shifted emissions.…”