Glutathione-activated biotin-targeted dual-modal imaging probe with improved PDT/PTT synergistic therapy.

BACKGROUND: Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. RESULTS: In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. SIGNIFICANCE: A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

Tumor-Targeting Probe for Dual-Modal Imaging of Cysteine In Vivo.

Cysteine (Cys) is a crucial biological thiol that has a vital function in preserving redox homeostasis in organisms. Studies have shown that Cys is closely related to the development of cancer. Thus, it is necessary to design an efficient method to detect Cys for an effective cancer diagnosis. In this work, a novel tumor-targeting probe (Bio-Cy-S) for dual-modal (NIR fluorescence and photoacoustic) Cys detection is designed. The probe exhibits high selectivity and sensitivity toward Cys. After reaction with Cys, both NIR fluorescence and photoacoustic signals are activated. Bio-Cy-S has been applied for the dual-modal detection of Cys levels in living cells, and it can be used to distinguish normal cells from cancer cells by different Cys levels. In addition, the probe is capable of facilitating dual-modal imaging for monitoring changes in Cys levels in tumor-bearing mice. More importantly, the excellent tumor-targeting ability of the probe greatly improves the signal-to-noise ratio of imaging. To the best of our knowledge, this is the first Cys probe to combine targeting and dual-modal imaging performance for cancer diagnosis.

Near-Infrared Fluorescent Probe with Large Stokes Shift for Imaging of Hydrogen Sulfide in Tumor-Bearing Mice.

Hydrogen sulfide (H2S) is an important endogenous gas signal molecule in living system, which participates in a variety of physiological processes. Very recent evidence has accumulated to show that endogenous H2S is closely associated with various cancers and can be regarded as a biomarker of cancer. Herein, we have constructed a new near-infrared fluorescent probe (DCP-H2S) based on isophorone-xanthene dye for sensing hydrogen sulfide (H2S). The probe shows remarkable NIR turn-on signal at 770 nm with a large Stokes shift of 200 nm, together with high sensitivity (15-fold) and rapid detection ability for H2S (4 min). The probe also possesses excellent selectivity for H2S over various other analytes including biothiols containing sulfhydryl (-SH). Moreover, DCP-H2S has been successfully applied to visualize endogenous and exogenous H2S in living cells (293T, Caco-2 and CT-26 cells). In particular, the excellent ability of DCP-H2S to distinguish normal mice and tumor mice is shown, and it is expected to be a powerful tool for detection of H2S in cancer diagnosis.