CN-122010837-A - Preparation method and application of polarity and viscosity dual-response type NIR-II fluorescent probe

Abstract

The invention belongs to the technical field of fluorescent probes, and particularly relates to a polar and viscosity dual-response type NIR-II fluorescent probe, a preparation method thereof and a structural formula using the probe, wherein the structural formula is as follows: The invention provides a method for synthesizing a near infrared two-region fluorescence emission probe by taking 5-tertiary butyl-2-chloro-3-hydroxycyclohexa-1-ene-1-formaldehyde and 6-bromo-2-methyl-1-ethylquinoline-1-onium as raw materials. The probe can detect polarity and viscosity with high sensitivity and high selectivity, has photo-thermal treatment effect, can emit fluorescence in near infrared two regions, and has good photo-thermal killing effect on breast cancer cells. The probe provides an accurate tool for polarity and viscosity detection and tumor diagnosis and treatment in the biomedical field, and is expected to be widely applied in disease diagnosis and drug research and development.

Inventors

• Ouyang juan
• YAN YING
• LI CHUNYAN

Assignees

• 湘潭大学

Dates

Publication Date

20260512

Application Date

20260312

Claims (5)

1. 1. A polarity and viscosity dual-response type NIR-II fluorescent probe is characterized by comprising the following chemical structure:
2. 2. The method for preparing the polar and viscosity dual-response type NIR-II fluorescent probe according to claim 1, wherein the synthetic route is as follows:
3. 3. The method for preparing the polar and viscosity dual-response type NIR-II fluorescent probe according to claim 2, comprising the following reaction steps: 6-bromo-1-ethyl-2-methylquinolin-1-ium salt and 5-tert-butyl-2-chloro-3-hydroxycyclohex-1-ene-1-carbaldehyde were added to a round-bottomed flask and dissolved in n-butanol as a solvent, followed by addition of piperidine, heating to 110℃and stirring to react for 12 hours. After the reaction, the solvent is removed by a rotary evaporator, and the fluorescent probe is obtained by purifying the solvent by silica gel column chromatography, wherein the eluent is dichloromethane, methanol=10:1, and thus the dark red solid is obtained.
4. 4. The method for preparing a polar and viscometric dual response type NIR-II fluorescent probe according to claim 2, characterized in that the molar ratio of 6-bromo-1-ethyl-2-methylquinolin-1-ium salt to 5-tert-butyl-2-chloro-3-hydroxycyclohex-1-ene-1-carbaldehyde is 3:1.
5. 5. The use of a polar and viscometric dual response NIR-II fluorescent probe according to claim 1, wherein said fluorescent probe has two bromine atoms, exhibits excellent photodynamic therapy effect, and is effective in killing cancer cells.

Description

Preparation method and application of polarity and viscosity dual-response type NIR-II fluorescent probe Technical Field The invention belongs to the technical field of fluorescent probes, and particularly relates to a polarity and viscosity dual-response type NIR-II fluorescent probe, and a preparation method and application thereof. Background Breast cancer is the most common cancer in women worldwide, with morbidity and mortality leading among female cancers, which severely threatens female health and life .（Liu X. H., Wang Z. C., Shen L., Shen S. L., and Zhang X. F. Viscosity-Responsive Cell-Membrane-Anchored Fluorescent Probe for Visualization of Tumor Cell Membranes and Tumors. Analytical Chemistry, 2025, 97, 26759-26769）. clinical management of pre-breast cancer lesions and malignant lesions places a significant burden on the health system. Despite significant advances in the diagnosis and treatment of breast cancer, there remains a need for reliable biomarkers to further refine screening, triage and management work in women. In recent years, accurate diagnosis of cancer by means of change in the microenvironment of cancer cells has become a popular field of research. Under the stimulation of a particular biological environment associated with cancer cells, fluorescent probes are activated or quenched, and such probes are capable of responding to changes in subcellular microenvironments, such as viscosity, polarity, pH, oxygen content, etc., which have been considered as key biomarkers （Qian M., Ye Y., Ren T. B., Xiong B., Yuan L., and Zhang X. B. Cancer-Targeting and Viscosity-Activatable Near-Infrared Fluorescent Probe for Precise Cancer Cell Imaging. Analytical Chemistry, 2024, 96, 13447-13454）. for cancer progression, wherein viscosity, an important parameter in the cellular microenvironment, affects signal transduction, metabolite diffusion, and biomolecular interactions. Tumor-associated increases in viscosity are associated with increased lactate production and protein, enzyme and lipid levels. Polarity is another critical microenvironment parameter that plays an important role in maintaining cellular homeostasis, and abnormalities often closely correlate with cellular dysfunction and cancer, and abnormalities in （Narotamo H., Franco C. A., Silveira M. 3D CellPol: Joint Detection and Pairing of Cell Structures to Compute Cell Polarity. Biomedical Signal Processing and Control, 2025, 104, 107537）. viscosity and polarity are closely correlated with cellular dysfunction and cancer. Thus, monitoring cancer biomarkers can provide a potential strategy for accurate diagnosis and treatment of cancer. The near infrared two-region (NIR-II) fluorescent imaging probe can effectively reduce photon scattering and autofluorescence phenomena by virtue of the longer emission wavelength (900-1700 nm) of the near infrared two-region (NIR-II) fluorescent imaging probe, so that the penetration capability of deep tissues and the imaging resolution （Xu L. Z., Zhang Q., Wang X., Lin W. Y. Biomedical Applications of NIR-II Organic Small Molecule Fluorescent Probes in Different Organs. Coordination Chemistry Reviews, 2024, 519, 216122）. of the existing NIR-II probe are improved, the existing NIR-II probe is in a normal bright mode or responds to only a single stimulus, the signal to noise ratio is low, and the potential false positive problem （Dou K., Lu J., Xiu Y. L, Wang R., Won M., Kim J., Yu F. B., and Kim J. S. Metabolic Acidity/H2O2 Dual-Cascade-Activatable Molecular Imaging Platform toward Metastatic Breast Tumor Malignancy. Angewandte Chemie International Edition, 2024, 64, e202419191）. is caused, so that the fluorescent probe with the capability of detecting multiple biomarkers in a single system has obvious advantages, such as the capability of reducing the complexity of a detection process and ensuring the consistency of in vivo localization and metabolism. Multiple biomarker responsive fluorescent probes are receiving great attention because of their ability to increase detection specificity and enable multiplex analysis. The mode can reduce the occurrence of false positive conditions, improve imaging resolution （Deng M., Wang P. P., Zhai Z. B., Liu Y., Cheng D., He L. W., and Li S. J．A Triple-Responsive and Dual-NIR Emissive Fluorescence Probe for Precise Cancer Imaging and Therapy by Activating Pyroptosis Pathway. Analytical Chemistry, 2025, 97, 2998-3008）., and the expression of polarity and viscosity in breast cancer cells is different from that of normal cells, so that the characteristic of the mode makes the mode a reliable microenvironment marker. Based on abnormal expression of polarity and viscosity, the NIR-II fluorescent probe can be accurately activated in an anoxic tumor environment, and targeted imaging of breast cancer is realized, so that higher diagnosis sensitivity and accuracy are provided. Therefore, the reasonable design and synthesis of the polarity and viscosity dual-response NIR-II f