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CN-121974927-A - Self-assembled fluorescent probe and preparation method and application thereof

CN121974927ACN 121974927 ACN121974927 ACN 121974927ACN-121974927-A

Abstract

The invention discloses a self-assembled fluorescent probe and a preparation method and application thereof. According to the invention, 1-ethyl-2-methylbenzo [ cd ] indol-1-onium is added into a mixed solution of 10- [4- (dimethylamino) phenyl ] -7-phenyl-3, 11-dithio-7-azatricyclo [6.3.0.02,6] undecane-1 (8), 2 (6), 4, 9-tetraene-4-formaldehyde, acetic acid, acetic anhydride and triethylamine, and then mixed with methyl tertiary butyl ether to obtain micromolecule DMA-IN3, and then the micromolecule DMA-IN3 is subjected to ultrasonic self-assembly to obtain nano-particles DINP. The self-assembled fluorescent probe DINP has fluorescent property and phototoxicity, can be targeted and enriched to tumor tissues, generates a large amount of heat under illumination condition, realizes the visual diagnosis and treatment of tumors, has good biological safety, and provides a new scheme for clinical tumor treatment.

Inventors

  • SUN JIANBO
  • Zha Menglei
  • LIANG YONGYE
  • WANG XINYUAN

Assignees

  • 东莞市东南部中心医院(东莞市东南部中医医疗服务中心、广东医科大学附属东莞第一医院)

Dates

Publication Date
20260505
Application Date
20251229

Claims (9)

  1. 1. The self-assembled fluorescent probe is characterized in that the structural formula of the fluorescent probe is shown as formula I: Formula I.
  2. 2. The self-assembled fluorescent probe of claim 1, wherein the fluorescent probe has a molecular particle size of 50-100 nm.
  3. 3. The method for preparing a self-assembled fluorescent probe according to any one of claims 1 to 2, comprising the steps of: S1, adding 1-ethyl-2-methylbenzo [ cd ] indol-1-ium into a mixed solution of acetic acid, acetic anhydride and triethylamine of 10- [4- (dimethylamino) phenyl ] -7-phenyl-3, 11-dithio-7-azatricyclo [6.3.0.02,6] undec-1 (8), 2 (6), 4, 9-tetraene-4-formaldehyde, and stirring; s2, adding methyl tertiary butyl ether into the mixture, filtering and collecting a filter cake, and concentrating under reduced pressure to obtain a crude product; S3, purifying by column chromatography, grinding with ethyl acetate and freeze-drying to finally obtain 4- [10- [ (E) -2- (1-ethylbenzo [ cd ] indol-1-onium-2-yl) vinyl ] -7-phenyl-3, 11-dithiol-7-azatricyclo [6.3.0.02,6] undec-1 (8), 2 (6), 4, 9-tetraen-4-yl ] -N, N-dimethylaniline; s4, carrying out ultrasonic treatment on the obtained chemical molecules to obtain the self-assembled fluorescent probe.
  4. 4. A method of preparation according to claim 3 wherein the temperature of the agitation is 60 ℃ for a period of time of 10 to 16 h.
  5. 5. The method according to claim 3, wherein the eluent for column chromatography purification is a mixed reagent of dichloromethane and methanol, and the volume ratio is dichloromethane: methanol=10:0 to 10:1 linear gradient elution, rf=0.42.
  6. 6. The process according to claim 3, wherein the volume ratio of acetic acid to acetic anhydride to triethylamine is 10:1:1, and the molar ratio of 10- [4- (dimethylamino) phenyl ] -7-phenyl-3, 11-dithio-7-azatricyclo [6.3.0.02,6] undec-1 (8), 2 (6), 4, 9-tetraene-4-carbaldehyde to 1-ethyl-2-methylbenzo [ cd ] indol-1-ium is 1:2.5.
  7. 7. A method of preparing according to claim 3, wherein the ultrasound is at a power of 30-60w for a time of 2-4 min.
  8. 8. A pharmaceutical composition for detecting and/or treating a tumor comprising the fluorescent probe of claim 1.
  9. 9. The pharmaceutical composition of claim 8, wherein the tumor comprises any one of breast cancer, ovarian cancer, colorectal cancer.

Description

Self-assembled fluorescent probe and preparation method and application thereof Technical Field The invention relates to the field of nanoparticle synthesis and application, in particular to a self-assembled fluorescent probe and a preparation method and application thereof. Background Early accurate diagnosis of tumors has been a significant challenge in clinical medicine. Traditional imaging methods such as CT, MRI, etc. while capable of providing macroscopic anatomical information, have significant limitations in detecting millimeter-scale micro-lesions and in real-time intra-operative navigation. The fluorescence imaging technology provides a solution to the difficult problem by virtue of the advantages of high sensitivity, real-time imaging, no radiation and the like of the 1 mm-level focus detection. Especially near infrared (NIR, 700-1700 nm) fluorescence imaging, the tissue penetration depth is deeper and can reach 5-10 mm, the self fluorescence interference is small, and the imaging has become a research hot spot for navigation in oncology. Molecular fluorescent probes can be divided into two categories, namely small molecular probes and nano probes according to the structural characteristics of the molecular fluorescent probes. The small molecular probe has the advantages of clear chemical structure, clear metabolic path, good tissue penetrability and the like, but has the problems of short blood circulation time and low tumor accumulation efficiency. While nanoprobes have long circulation times and enhanced retention effects, they face challenges such as uncertain chemical structures, difficult metabolism, potential toxicity, and difficulty in penetrating deep tissues. The self-assembled molecular technology refers to the process of forming an ordered nano structure by spontaneous organization of a small molecular probe under a specific stimulation condition, and provides an innovative thought for overcoming the limitation. Clinical data shows that fluorescence navigation techniques based on self-assembly strategies have achieved significant success. For example, ICG navigation can increase the incisional negative rate of breast cancer surgery to 92%, whereas 5-ALA has a fluorescence positive predictive value of 85% in glioblastoma surgery. In the prior art, a plurality of fluorescent probes for tumor detection have the problem of limited fluorescence penetration depth, and the probes with excellent fluorescence performance in the near infrared two regions have poor phototoxicity, so that the tumor treatment is difficult to realize. The project is to use molecular engineering design to obtain a small molecular photosensitive probe capable of self-assembling, so that the small molecular photosensitive probe has fluorescence performance and phototoxicity, and is targeted to enrich tumor tissues, thereby realizing the visual diagnosis and treatment of tumors. Disclosure of Invention Aiming at the defects in the prior art, the invention provides a self-assembled fluorescent molecular probe, and a preparation method and application thereof. The invention provides a self-assembled fluorescent probe, the structural formula of which is shown as formula I: Formula I. The fluorescent probe generates active oxygen clusters and heat under illumination, and the 808 nm laser irradiates the fluorescent probe to generate a large amount of active oxygen clusters and heat. Further, the molecular particle size of the fluorescent probe is 50-100 nm, the particle size of the self-assembled fluorescent probe is detected by a particle size meter, the particle size is 50-100 nm, and the average particle size is 74.32 nm. The invention also provides a preparation method of the self-assembled fluorescent probe, which comprises the following steps: S1, adding 1-ethyl-2-methylbenzo [ cd ] indol-1-ium into a mixed solution of acetic acid, acetic anhydride and triethylamine of 10- [4- (dimethylamino) phenyl ] -7-phenyl-3, 11-dithio-7-azatricyclo [6.3.0.02,6] undec-1 (8), 2 (6), 4, 9-tetraene-4-formaldehyde, and stirring; s2, adding methyl tertiary butyl ether into the mixture, filtering, collecting a filter cake, and concentrating under reduced pressure to obtain a crude product; S3, purifying by column chromatography, grinding with ethyl acetate and freeze-drying to finally obtain 4- [10- [ (E) -2- (1-ethylbenzo [ cd ] indol-1-onium-2-yl) vinyl ] -7-phenyl-3, 11-dithiol-7-azatricyclo [6.3.0.02,6] undec-1 (8), 2 (6), 4, 9-tetraen-4-yl ] -N, N-dimethylaniline; s4, carrying out ultrasonic treatment on the obtained chemical molecules to obtain the self-assembled fluorescent probe. Further, the temperature of the stirring is 60 ℃ and the time is 10-16 h. Further, the eluent for column chromatography purification is a mixed reagent of dichloromethane and methanol, wherein the volume ratio is linear gradient elution of dichloromethane: methanol=10:0 to 10:1, and rf=0.42. Further, the volume ratio of acetic anhydride to triethylamin