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CN-117089338-B - Preparation method of novel near infrared light diagnosis and treatment agent based on anthrone purple derivative

CN117089338BCN 117089338 BCN117089338 BCN 117089338BCN-117089338-B

Abstract

The invention discloses a preparation method of a novel near infrared light diagnosis and treatment agent based on anthrone purple derivatives, which comprises the following steps of adding K 2 CO 3 into a N, N-Dimethylformamide (DMF) solution of 16, 17-dihydroxyanthrone purple under heating condition, dehydrogenating, adding [1- (4-bromomethylphenyl) -1, 2-triphenyl ] ethylene into a reaction solution, raising the temperature to react for 12 hours, settling and filtering an S1 reaction product by methanol and water, separating a crude product by a silica gel column chromatography by using dichloromethane and ethyl acetate as eluent, performing spin steaming and drying to obtain a dark blue tetrastyrene modified anthrone purple derivative, and realizing water solubility of the molecule by using mesoporous silica or an amphiphilic polymer to wrap the molecule to obtain the corresponding light diagnosis and treatment agent. The method is simple to operate, the obtained material can emit 700-1200nm fluorescence after being excited by near infrared one-area laser, singlet oxygen and hydroxyl free radicals are simultaneously generated for photodynamic therapy, and mesoporous silica coating can also be used for drug loading and transport.

Inventors

  • LU FENG
  • Ge Yinrui
  • WANG ZHEN
  • WANG QI
  • FAN QULI

Assignees

  • 南京邮电大学

Dates

Publication Date
20260512
Application Date
20230804

Claims (7)

  1. 1. The preparation method of the novel near infrared light diagnosis and treatment agent based on the anthrone purple derivative is characterized by comprising the following steps of: S1, preparing a 0.125 mol/L16, 17-dihydroxyanthrone purple dimethylformamide solution, adding K 2 CO 3 with the molar ratio being 4 times of the dimethylformamide solution as a catalyst, heating to 80 ℃ for reaction for 30min, adding [1- (4-bromomethylphenyl) -1, 2-triphenyl ] ethylene with the molar ratio being 3 times of the dimethylformamide solution, heating to 100 ℃, and continuously reacting for 12h; s2, settling the reaction product of S1 by using methanol and water, filtering after settling for 24 hours to obtain a solid crude product, separating by using dichloromethane and ethyl acetate as eluent through silica gel column chromatography, and obtaining a dark blue tetraphenyl ethylene modified anthrone purple derivative after rotary evaporation and drying; And S3, realizing the water solubility of the deep blue tetraphenyl ethylene modified anthrone purple derivative by using mesoporous silica or an amphiphilic polymer to wrap, thereby obtaining the photodiagnosis and treatment agent.
  2. 2. The method for preparing the novel near infrared light diagnosis and treatment agent based on the anthrone purple derivative, which is disclosed in claim 1, is characterized in that in S2, the volume ratio of methanol to water is 3:2, and the volume ratio of dichloromethane to ethyl acetate is 50:1.
  3. 3. The method for preparing a novel near-infrared light diagnosis and treatment agent based on the anthrone purple derivative according to claim 1, wherein in the step S3, the step of obtaining the light diagnosis and treatment agent by using mesoporous silica comprises the following steps: Preparing 1mg/mL of chloroform solution of the tetraphenyl ethylene modified anthrone purple derivative, mixing the chloroform solution with 20mg/mL of hexadecyl trimethyl ammonium bromide aqueous solution, removing chloroform under the heating condition of 60 ℃ after ultrasonic emulsification to obtain a first aqueous solution, mixing the first aqueous solution with water, tetraethoxysilane, ethyl acetate and 2mol/L sodium hydroxide aqueous solution, reacting for 30min at 70 ℃, adding triethoxysilane modified polyethylene glycol, continuing to react for 2.5h, and obtaining the water-soluble anthrone purple-mesoporous silica nanoparticle photodiagnosis and treatment agent after ultrafiltration purification.
  4. 4. The method for preparing a novel near-infrared diagnostic and therapeutic agent based on an anthrone purple derivative according to claim 1, wherein in the step S3, the step of obtaining the diagnostic and therapeutic agent by using an amphiphilic polymer comprises the following steps: And (3) dissolving the tetrastyrene modified anthrone purple derivative obtained in the step (S2) and the amphiphilic polymer surfactant in a mixed solvent of chloroform and tetrahydrofuran, adding the mixed solvent into water with the volume of 10 times of that of the mixed solvent under an ultrasonic condition, and blowing off an organic solvent by using nitrogen under a heating condition of 50 ℃ to obtain the polymer-coated water-soluble anthrone purple nanoparticle photodiagnosis and treatment agent.
  5. 5. The method for preparing a novel near infrared light diagnosis and treatment agent based on an anthrone purple derivative according to claim 3, wherein the volume ratio of the first aqueous solution to the water, tetraethoxysilane, ethyl acetate and 2mol/L sodium hydroxide aqueous solution is 1:9:0.04:0.2:0.06.
  6. 6. The method for preparing a novel near-infrared diagnostic and therapeutic agent based on an anthrone purple derivative according to claim 4, wherein the volume ratio of chloroform to tetrahydrofuran is 1:1.
  7. 7. The method for preparing a novel near-infrared light diagnosis and treatment agent based on an anthrone purple derivative according to claim 4, wherein the amphiphilic polymer surfactant comprises at least one of PluronicF-127 and DSPE-PEG.

Description

Preparation method of novel near infrared light diagnosis and treatment agent based on anthrone purple derivative Technical Field The invention belongs to the technical field of near infrared light emitting and phototherapy materials, and particularly relates to a preparation method of a novel near infrared light diagnosis and treatment agent based on an anthrone purple derivative. Background Near infrared fluorescence imaging technology is a rapid high-resolution detection technology which is rapidly raised in the biomedical field in recent years, and is rapidly used for researching diseases such as tumors. The development of optical imaging technology has not been separated from the design and development of high performance optical contrast agents. The common optical contrast agent mainly comprises organic small molecules, inorganic nano materials, conjugated high polymer materials and the like. Among them, the organic small molecule is an optical contrast agent with the prospect of clinical application because of the advantages of fixed structure, good metabolizability, low toxicity and the like. At present, clinically used organic small molecules such as ICG, MB and the like have the defects of poor light stability, low fluorescence quantum yield and the like. Meanwhile, diagnosis and treatment integration is the front edge of research in the related field at present, and the efficiency of ICG, MB and other molecules in photodynamic therapy is also poor. Therefore, the development of novel organic small molecular materials with high light stability, high near infrared two-region fluorescence intensity and outstanding photodynamic treatment effect is needed, which has important significance in the field of optical diagnosis and treatment. Anthrone violet is a type of vat dye commonly used in the textile field, has outstanding light stability and low toxicity, and particularly methylated dimethyl xanthone violet, namely vat brilliant green B, accounts for a large proportion in yarn dyeing. However, these dyes have poor water solubility, low fluorescence intensity, and no obvious active oxygen production capability, and cannot be directly applied to the field of biological diagnosis and treatment. In view of the above, it is necessary to design a method for preparing a novel near infrared diagnostic agent based on an anthrone violet derivative to solve the above problems. Disclosure of Invention The invention aims to provide a preparation method of a novel near infrared light diagnosis and treatment agent based on an anthrone purple derivative. In order to achieve the above purpose, the present invention adopts the following technical scheme: S1, preparing a 0.125 mol/L16, 17-dihydroxyanthrone purple dimethylformamide solution, adding K 2CO3 with the molar ratio being 4 times of the dimethylformamide solution as a catalyst, heating to 80 ℃ for reaction for 30min, adding [1- (4-bromomethylphenyl) -1, 2-triphenyl ] ethylene with the molar ratio being 3 times of the dimethylformamide solution, heating to 100 ℃, and continuously reacting for 12h; s2, settling the reaction product of S1 by using methanol and water, filtering after settling for 24 hours to obtain a solid crude product, separating by using dichloromethane and ethyl acetate as eluent through silica gel column chromatography, and obtaining a dark blue tetraphenyl ethylene modified anthrone purple derivative after rotary evaporation and drying; And S3, realizing the water solubility of the deep blue tetraphenyl ethylene modified anthrone purple derivative by using mesoporous silica or an amphiphilic polymer to wrap, thereby obtaining the photodiagnosis and treatment agent. As a further improvement of the invention, in the S2, the volume ratio of the methanol to the water is 3:2, and the volume ratio of the dichloromethane to the ethyl acetate is 50:1. In the step S3, the step of obtaining the photodiagnosis and treatment agent by using mesoporous silica comprises the following steps of: Preparing 1mg/mL of chloroform solution of the tetraphenyl ethylene modified anthrone purple derivative, mixing the chloroform solution with 20mg/mL of hexadecyl trimethyl ammonium bromide aqueous solution, removing chloroform under the heating condition of 60 ℃ after ultrasonic emulsification to obtain a first aqueous solution, mixing the first aqueous solution with water, tetraethoxysilane, ethyl acetate and 2mol/L sodium hydroxide aqueous solution, reacting for 30min at 70 ℃, adding triethoxysilane modified polyethylene glycol, continuing to react for 2.5h, and obtaining the water-soluble anthrone purple-mesoporous silica nanoparticle photodiagnosis and treatment agent after ultrafiltration purification. In the S3, the step of obtaining the photodiagnosis and treatment agent by using the amphiphilic polymer comprises the following steps of: Dissolving the tetrastyrene modified anthrone purple derivative obtained in the step S2 and an amphiphilic polymer surfactan