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

L-Cysteine, distinguished by its possession of reactive sulfhydryl groups within its molecular structure, plays a significant role in both biological systems and the pharmaceutical industry. It stands not only as a natural component integral to the constitution of glutathione but also as the principal precursor for the synthesis of L-cystine through an oxidation reaction. This study endeavors to introduce a novel approach to L-cysteine analysis, capitalizing on its optical activity, whereby an optical rotation detection system grounded in the principles of quantum weak measurement is proffered. The optical rotation angle corresponding to the concentration of chiral solutions can be accurately ascertained through spectral analysis. In practical implementation, a chiral sensing system, boasting a sensitivity of 372 nm/rad, was meticulously constructed, leveraging the concept of weak value amplification. Then, the real-time monitoring of chemical reactions involving L-cysteine and dimethyl sulfoxide was performed. Under the specific experimental conditions outlined in this investigation, it was observed that the oxidation process culminated within approximately 12 h. The application of weak measurement-based chiral sensors holds immense potential, providing robust technical support for real-time monitoring in fields such as chiral analysis and the synthesis of chiral pharmaceutical compounds.

Section: Introductionmentioning

confidence: 99%

Oxidation Analysis of l-Cysteine with a Chiral Sensor Based on Quantum Weak Measurement

Zhang,

Chen,

Weng

et al. 2024

“…Therefore, NIR fluorescent/PA bimodal imaging is suitable and desired for studying in vivo ferroptosis. Despite the progress in developing probes for NIR fluorescent/PA bimodal imaging of Cys or other biothiols, − the changes in the concentration of biothiols such as Cys and GSH in ferroptosis of PADC have not yet been explored by imaging manner (Table S1). Thus, there is still an urgent need to construct novel imaging probes for monitoring Cys and total biothiol levels in in vivo ferroptosis, which is quite important for understanding the mechanism of PDAC ferroptosis and promoting the treatment of PDAC.…”

Section: Introductionmentioning

confidence: 99%

NIR Fluorescent/Photoacoustic Bimodal Imaging of Ferroptosis in Pancreatic Cancer Using Biothiols-Activable Probes

Li,

Zhang,

Zhou

et al. 2024

Self Cite

Ferroptosis modulation is a powerful therapeutic option for pancreatic ductal adenocarcinoma (PDAC) with a low 5year survival rate and lack of effective treatment methods. However, due to the dual role of ferroptosis in promoting and inhibiting pancreatic tumorigenesis, regulating the degree of ferroptosis is very important to obtain the best therapeutic effect of PDAC. Biothiols are suitable as biomarkers of imaging ferroptosis due to the dramatic decreases of biothiol levels in ferroptosis caused by the inhibited synthesis pathway of glutathione (GSH) and the depletion of biothiol by reactive oxygen species. Moreover, a very recent study reported that cysteine (Cys) depletion can lead to pancreatic tumor ferroptosis in mice and may be employed as an effective therapeutic strategy for PDAC. Therefore, visualization of biothiols in ferroptosis of PDAC will be helpful for regulating the degree of ferroptosis, understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis, and further promoting the study and treatment of PDAC. Herein, two biothiol-activable near-infrared (NIR) fluorescent/photoacoustic bimodal imaging probes (HYD-BX and HYD-DX) for imaging of pancreatic tumor ferroptosis were reported. These two probes show excellent bimodal response performances for biothiols in solution, cells, and tumors. Subsequently, they have been employed successfully for real-time visualization of changes in concentration levels of biothiols during the ferroptosis process in PDAC cells and HepG2 cells. Most importantly, they have been further applied for bimodal imaging of ferroptosis in pancreatic cancer in mice, with satisfactory results. The development of these two probes provides new tools for monitoring changes in concentration levels of biothiols in ferroptosis and will have a positive impact on understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis and further promoting the study and treatment of PDAC.

“…Photoacoustic (PA) tomography, as a noninvasive and nonionizing imaging modality, has a wide range of clinical applications, including cancer detection, vascular imaging, neuroimaging, and monitoring of metabolic processes. − Compared with traditional optical sensing, − PA tomography provides a deeper tissue penetration and a higher spatial resolution for in vivo imaging via circumventing the strong light scattering of tissue. − Given this, some disease-associated stimuli (e.g., pH, ROS, RSS, and enzymes) have been used to construct PA probes, to visualize and detect the biomarker of interest at the molecular level in a noninvasive manner. − Among them, RSS, specifically Cys or H 2 S-activatable PA probes have been developed and found widespread applications in tumor imaging. − However, the current single-locked molecular probes for RSS PA sensing might produce false positive signals in a complex biological system, failing to precisely distinguish RSS-associated diseases.…”

mentioning

confidence: 99%

An AND-Gate Photoacoustic Probe for Cys and H₂S Precise Photoacoustic Sensing in Localized Tumors

Li,

et al. 2024

Photoacoustic (PA) tomography has shown many promising aspects in noninvasive and precise imaging of deep-localized biomarkers. However, these traditional single-locked PA probes always face challenges in precise PA imaging with high specificity. Here, we report a novel AND-gate photoacoustic probe, BAE, to improve tumor imaging accuracy via the combination of two tumor-associated biomarkers, cysteine (Cys) and hydrogen sulfide (H 2 S). Only when Cys and H 2 S are concurrently introduced into the detection system does the absorption of BAE red-shift from the initial 680 to 810 nm, thereby showing a 5.29-fold enhancement in its PA signal at 810 nm. The good specificity of BAE is proven, since an obvious PA signal could be observed only in the solution containing both Cys and H 2 S and was not affected by other reactive sulfur species. After being taken up by tumors with the assistance of a nanomicelle, the AND-gate PA probe BAE was applied for dynamic real-time monitoring of Cys and H 2 S in vivo, achieving precise identification of tumors. This AND-gate PA probe provides a potential technical tool for precise sensing analysis of deep-seated diseases.