Application of near-infrared weightless atom Bodipy to photodynamic therapy of metastatic tumor and upconversion

A technology for photodynamic therapy and fluoroboropyrrole, which is applied in the field of fluoroboropyrrole-based photodynamic therapy reagents for tumor/metastasis tumors and up-conversion reagents, photodynamic therapy reagents and up-conversion reagents, and can solve the problem of weak up-conversion luminescence, weak up-conversion luminescence, and up-conversion reagents. The toxicity and biosafety of inorganic upconversion nanoparticles are unclear, and the upconversion efficiency is low, which can achieve the effect of high-efficiency photodynamic therapy, good tissue penetration, and easy synthesis.

Pending Publication Date: 2020-08-11
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most of these upconversion systems are inorganic upconversion nanoparticles (UCNPs) doped with lanthanide metal ions. [13] However, the inorganic upconversion nanoparticles doped with lanthanide metal ions have extremely low upconversion effic

Method used

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  • Application of near-infrared weightless atom Bodipy to photodynamic therapy of metastatic tumor and upconversion
  • Application of near-infrared weightless atom Bodipy to photodynamic therapy of metastatic tumor and upconversion
  • Application of near-infrared weightless atom Bodipy to photodynamic therapy of metastatic tumor and upconversion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] [Example 1] Preparation of BDP-helix

[0059] (1) Synthetic references of the compounds were synthesized. [16] Mix fluoroborate pyrrole dye 1 (100mg, 0.175mmol) containing iodine atom at the 2 and 6 positions with o-formylphenyl boronate 2 (80mg, 0.52mmol), add tetrabutylammonium bromide (60mg, 0.17mmol) As a phase transfer catalyst, it was dissolved in 20 mL of tetrahydrofuran solvent under the protection of inert gas, and tetrakis(triphenylphosphine) palladium catalyst (0.017-0.035 mmol) was added. 6 mL of 2M aqueous sodium carbonate solution was added, and the reaction was heated at 80° C. for 1.5 h (monitoring the progress of the reaction by TLC to avoid deterioration of the product). After the reaction, the reaction solution was cooled to room temperature, and the solvent was distilled off. Then an organic solvent of dichloromethane was added, washed with saturated brine (3×20 mL), and dried over anhydrous magnesium sulfate or anhydrous sodium sulfate. Separatio...

Embodiment 2

[0061] [Example 2] Preparation of BDP-helix-NP

[0062] (1) Preparation of polymer PSMA-PEG-OA: PSMA (160mg) and PEG 2000 -NH 2 (200 mg) was dissolved in 30 mL of dry tetrahydrofuran solvent. Heated at 70°C for 5h under nitrogen protection. Octadecylamine (26 mg) was dissolved in 5 mL of dry THF, and slowly added to the above mixture within 30 min. Continue stirring at 70°C for 5h. After the reaction, the reaction solution was stored at a low temperature at 4°C.

[0063]

[0064] (2) Dissolve 0.5 mg of BDP-helix and 30 mg of PSMA-PEG-OA in 2 mL of THF, and add 10 mL of PBS buffer solution (pH=7.24). The mixture was stirred at 40 °C for 2 h. After the reaction solution was cooled to room temperature, it was dialyzed with deionized water for 24h to obtain BDP-helix-NP (such as figure 1 Shown in a) Store at 4°C at low temperature.

[0065] figure 1 In b is the dynamic light scattering test result of the BDP-helix-NP of the embodiment, and the test result shows that th...

Embodiment 3

[0066] [Example 3] Determination of BDP-helix-NP's ability to sensitize singlet oxygen and determination of cytotoxicity

[0067] (1) Ability to sensitize singlet oxygen: 10 5 CT26 tumor cells were cultured in a cell culture dish. After 12 hours of culture, a mixture of BDP-helix-NP (100nM, 2mL PBS buffer) and singlet oxygen fluorescent probe (SOSG, 5μM) was added, and the culture was continued for 4 hours. LED light source (20mW / cm 2 ) after 5min of light, the laser (λ ex = 488 nm) to detect changes in SOSG fluorescence. Use methylene blue as a standard reference compound (the singlet oxygen quantum yield of methylene blue in water is 60% [17] ), the measured singlet oxygen quantum yield of BDP-helix-NP (Φ Δ ) is 21%.

[0068] (2) In vitro cytotoxicity assay: the tumor cell CT26 cells were cultured on a 96-well plate, and BDP-helix-NP (0, 6.25, 12.5, 25, 50, 100 nM) were added after 24 hours, and the cells were incubated at 37°C and 5% CO 2 The incubation was continued ...

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Abstract

The invention discloses an application of near-infrared weightless atom Bodipy to photodynamic therapy of metastatic tumor and upconversion and belongs to the fine chemical engineering and life medical field. The reagent parent structure and nanoparticles thereof have very good photodynamic treatment effects. The nanoparticles are combined with immune drugs, and a tumor animal model verifies the outstanding metastatic tumor treatment effect. The photosensitive molecules are simple to synthesize and lower in cost, have high absorption capability in the long wavelength area and have super-long triplet state life and higher triplet state quantum yield. Given the excellent performance of the photosensitive molecules, the molecules are expected to become new generation photodynamic therapy reagents and metastatic tumor treatment reagents. Moreover, the invention also relates to a pure organic upconversion system containing no heavy atoms. Because of very high light absorbing capability of the photosensitive molecules, the photosensitive molecules can convert red light into very bright yellow upconversion light and have very high application potential in the biological field.

Description

technical field [0001] The invention relates to a class of fluoroboryrrole-based photodynamic therapy reagents for tumor / metastatic tumors and up-conversion reagents in the fields of fine chemical industry and life medicine. This type of photosensitive molecule can be used at a very low dose of reagent concentration (0.25μg / kg, far below the lowest clinical dose of 0.1mg / kg) and a lower light dose (6J / cm 2 ) to achieve high-efficiency photodynamic therapy effect and strong upconversion luminescence, which can enhance the effect of immunotherapy and synergistically treat metastatic tumors when used in combination with immunological drugs, and can be used for clinical photodynamic therapy and immune treat. The invention relates to the preparation of the matrix structure of the reagent and its nanoparticle, and it is used as a photodynamic therapy reagent and an up-converting reagent. The present invention particularly relates to the combined use of such reagent nanoparticles a...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/51A61K47/34A61K39/395A61P35/00A61P35/04C07F5/02
CPCA61K41/0057A61K9/5146A61K39/39558A61P35/00A61P35/04C07F5/022A61K2300/00
Inventor 赵建章闫雨欣王智佳黄灵
Owner DALIAN UNIV OF TECH
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