Dye‐Sensitized Downconversion Nanoprobes with Emission Beyond 1500 nm for Ratiometric Visualization of Cancer Redox State

Abstract

Detection of glutathione (GSH) in the body is essential to accurately map the redox state of cells and real‐time visualization of physiological and pathological conditions in vivo. However, traditional fluorescence (FL) imaging in the near‐infrared I region (NIR‐I, 650–900 nm) is difficult to quantitively visualize GSH in vivo due to the tissue autofluorescence background and disastrous photon scattering. Herein, a NIR‐IIb (1500–1700 nm) nanoprobe consisting of 4‐nitrophenol‐Cy7 (NPh) conjugated lanthanide‐based downconversion nanoparticles (DCNP@NPh‐PEG) is developed for in vivo ratiometric imaging of GSH. In the presence of GSH, NPh shows responsively enhanced FL emission at 808 nm, thus enhancing FL signal at 1550 nm of DCNPs excited by 808 nm (F1550, 808Ex) through non‐radiative energy transfer (NRET) effect, while the fluorescence of DCNP at 1550 nm excited by 980 nm laser (F1550, 980Ex) is stable because no NRET occurred. The ratiometric F1550, 980Ex/F1550, 808Ex value exhibits a linearship with GSH concentration ranged from 0–24 mm with detection limit of 0.3 mm. The NIR‐IIb nanoprobe has excellent performance in detecting and imaging GSH in both subcutaneous tumor and orthotopic colon tumor in vivo with high accuracy and resolution. The design strategy of the ratiometric NIR‐II FL nanoprobe based on the activated FERT effect provides a reliable tool for the development of NIR‐II nanoprobes for accurate biosensing in vivo.

In‐vivo two‐photon visualization and quantitative detection of redox state of cancer

“…The two R values (1.99 and 1.88) were substituted into the linear fitting curve in Figure 7D to obtain the corresponding GSH levels of 4.66 mM and 5.16 mM, respectively, which were consistent with the previously reported GSH levels in tumors (2-10 mM). [3,4]…”

“…This concentration is approximately 1000 times that of normal cells, making GSH a specific tumor marker. [ 3,4 ] Cancer cells produce large amounts of GSH as an antioxidant to protect themselves from external oxidative stress, such as reactive oxygen species (ROS)‐induced apoptosis. [ 5,6 ] GSH is actively involved in protecting cancer cells from apoptosis and plays a key role in the mechanism of drug resistance, primarily through the elimination of ROS from cells.…”

Near-Infrared-II Bioimaging for in Vivo Quantitative Analysis

“…Compared with normal tissue cells, the concentration of GSH in cancer cells was much higher, up to 2–10 mM, which was about 1,000 times higher than normal tissues/cells ( Barranco et al, 2000 ). Wang et al have modified the surface of core-shell down conversion nanoparticle (DCNPs) with 4-nitrophenol Cy7 (Nph) and amphiphilic distearyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) ( Wang et al, 2021b ). Due to the intramolecular photoinduced electron transfer (PET) process, the Nph molecules coated on the surface of DCNPs have no fluorescence.…”

“…Fortunately, the combination of superior NIR-II contrasts and advanced NIR-II bioimaging technologies can provide more detailed image parameters, which is suitable for in vivo quantitative analysis to understand biological process. In this review, we have summarized various types of NIR-II probes for in vivo quantitative analysis applications, including NIR-II fluorescence imaging ( Welsher et al, 2011 ; Wang F. et al, 2019 ; Yu et al, 2019 ; Liu et al, 2020c ; Tian et al, 2020 ), NIR-II ratiometric fluorescence/photoacoustic imaging ( Ye et al, 2020 ; Wang et al, 2021b ; Wang et al, 2021c ; Fu et al, 2021 ), and NIR-II fluorescence-lifetime imaging ( Fan et al, 2018 ; Zhao et al, 2020 ) for in vivo quantitative analysis, and also raised perspectives on potential challenges facing in this direction ( Figure 1 ).…”

Blue-LED-excitable NIR-II luminescent lanthanide-doped SrS nanoprobes for ratiometric thermal sensing

“…These outstanding features make Ln 3+ -doped NIR-II luminescent NCs ideal candidates as an alternative to traditional fluorescent probes like organic dyes and quantum dots and as a new generation of luminescent nanoprobes in many technological fields, including deep-tissue bioimaging, non-invasive chemical/biological detection, high-seed optical communication, and non-contact thermal sensing [10][11][12][13][14][15][16][17][18][19][20][21][22]. Nonetheless, because of the parity-forbidden nature of the 4f→4f electronic transitions, Ln 3+ -doped NIR-II luminescent NCs normally suffer from low absorption and emission efficiencies, and exhibit low-tomedium brightness when compared with organic dyes and quantum dots [23][24][25][26][27][28][29]. Therefore, a high-power laser is generally demanded to realize bright NIR-II luminescence in Ln 3+ -doped NCs, which may limit their widespread applications.…”