GSH-Activated Light-Up Near-Infrared Fluorescent Probe with High Affinity to α_vβ₃ Integrin for Precise Early Tumor Identification

Abstract

The development of tumor-associated, stimuli-driven, turn-on near-infrared (NIR) fluorophores requires urgent attention because of their potential in selective and precise tumor diagnosis. Herein, we describe a NIR fluorescent probe (CyA-cRGD) comprised of a fluorescence reporting unit (a cyanine dye) linked with a GSH-responsive unit (nitroazo aryl ether group) and a tumor-targeting unit (cRGD). The NIR fluorescence of CyA-cRGD with sensitive and selective response to GSH can act as a direct off-on signal reporter for GSH monitoring. Notably, CyA-cRGD possesses improved biocompatibility compared with CyA, which is highly desirable for in vivo fluorescence tracking of cancer. Confocal fluorescence imaging confirmed the tumor-targeting capability and GSH detection ability of CyA-cRGD in tumor cells, normal cells, and coincubated tumor /normal cells and in the three-dimensional multicellular tumor spheroid. Furthermore, it was validated that CyA-cRGD could detect tumor precisely in GSH and integrin αβ high-expressed tumor-bearing mouse models. Importantly, it was confirmed that CyA-cRGD possessed high efficiency for early-stage tumor imaging in mouse models with tumor cells implanted within 72 h. This method provided significant advances toward more in-depth understanding and exploration of tumor imaging, which may potentially be applied for clinical early tumor diagnosis.

Embryonic Stem Cells‐Derived Exosomes Endowed with Targeting Properties as Chemotherapeutics Delivery Vehicles for Glioblastoma Therapy

“…Direct modification of exosomes surface with tumor‐targeting ligand has been proved to be efficient in enhancing tumor retention of exosomes . Cyclo (Arg‐Gly‐Asp‐D‐Tyr‐Lys) peptide (c(RGDyK)) is a well‐known targeting ligand for cancer chemotherapy and exhibits high affinity with α v β 3 integrin receptors that over‐express on the surface of actively proliferating endothelium of tumor tissues such as GBM, prostate cancer, and lung cancer . These studies show that nanocarriers modified with c(RGDyK) can more efficiently deliver chemotherapeutic agents into cancer cells and could significantly improve antitumor effect.…”

A rational design of a cancer-specific and lysosome-targeted fluorescence nanoprobe for glutathione imaging in living cells

“…So far, much effort has gone into the development of unique GSH fluorescence probes. [26][27][28] However, most of them were either cancer cells-or subcellular organellespecific targeting GSH fluorescence probes; [29][30][31][32][33][34][35][36][37][38] however, single targeting systems were still unable to achieve efficient GSH detection. It is known that to realize the goal of efficiently detecting GSH in lysosome of specific cancer cells, an ideal GSH fluorescence probe should be constructed by combining specific cancer cell-and lysosome-targeting functions together with a GSH probe.…”

<p>Smart nanomedicine agents for cancer, triggered by pH, glutathione, H₂O₂, or H₂S</p>

“…In the presence of GSH, these reducible bonds can be cleaved, thus leading to the activation of the probe. For example, Yuan et al63 reported a GSH turn-on NIR fluorescent probe (CyA-cRGD), composed of a NIR fluorescence unit (CyA) binding with a fluorescence quenching unit (nitroazo aryl ether group) and a tumor-targeting unit (cRGD) (Figure 4A). With the presence of GSH, the nitroazo aryl ether group connecting the fluorescence unit and the fluorescence quenching unit will be cleaved, leading to the turn-on of the fluorescence (Figure 4B).…”