Application of nano sound sensitizer to preparing optoacoustic guidance-based acoustodynamic tumor treatment drugs

A technology of sonodynamics and tumor drugs, applied in the direction of anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of ineffective biological systems, limited stability of iridium complexes, complex methods, etc., and achieve sonodynamic therapy Enhanced effect, enhanced singlet oxygen yield, good dispersion effect

Inactive Publication Date: 2019-07-05
SHANGHAI NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In particular, due to the heavy atom effect of metal iridium, the fluorescence quantum yield is reduced, and the energy excited by the triplet state is released in the form of phosphorescence, or interacts with external oxygen molecules to produce singlet oxygen, or other types of active oxygen.
However, the stability of traditional iridium complexes still limits their application in biological systems. The improvement method is generally to introduce water-soluble groups to increase the compatibility of iridium complexes in organisms, or to wrap inorganic materials, generally silicon Material
The former method is more complicated and difficult to purify, while the latter has a small amount of metallic iridium, and the effect of applying it to biological systems is not obvious
In addition, the singlet oxygen yield of traditional sound sensitizers is low, and the general improvement method is to increase the oxygen source externally

Method used

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  • Application of nano sound sensitizer to preparing optoacoustic guidance-based acoustodynamic tumor treatment drugs
  • Application of nano sound sensitizer to preparing optoacoustic guidance-based acoustodynamic tumor treatment drugs
  • Application of nano sound sensitizer to preparing optoacoustic guidance-based acoustodynamic tumor treatment drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] IrPcCl as nano-acoustic sensitizer in the present invention 2 The preparation method of -BSA nanoparticles can be synthesized according to the method of Wang Jie's master's thesis of Shanghai Normal University, and the specific steps are as follows:

[0030] (1) Weigh [Ir(COD)Cl] 2 (161.82mg, 0.24mmol) and H 2Pc (218mg, 0.2mmol) was placed in a 100mL three-necked flask, vacuum-filled with nitrogen and circulated three times; 40mL of xylene was injected, and reacted at 155°C for 18h; a dark green solid was obtained by suction filtration; the solid was washed with anhydrous ether, filtered, and dried. Can obtain pure product 141mg, productive rate is about 52%; Among them, [Ir(COD)Cl] 2 for, H 2 Pc is 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-phthalocyanine.

[0031] (2) IrPcCl 2 -Preparation of BSA nanoparticles: First, the IrPcHCl 2 (2.70mg, 0.2mmol) dissolved in DMF (0.5mL), because DMF is an aprotic solvent, resulting in protic IrPcHCl 2 Due to the deprotonation ...

Embodiment 2

[0037] Verify the IrPcCl prepared by Example 1 2 -BSA nanoparticles simulate the performance of catalase to catalyze hydrogen peroxide to generate oxygen, and set the following three groups respectively:

[0038] The first group: the concentration of nanoparticles is 200 μM; the concentration of hydrogen peroxide is 0, 0.1, 0.5, 1.0, 5.0 and 10.0 (unit: mM), and the amount of oxygen produced within 15 minutes at 37° C. is measured.

[0039] The second group: the concentration of hydrogen peroxide is 10 mM; the concentration of nanoparticles is respectively 0, 50, 100, 150 and 200 (unit: μM), and the amount of oxygen produced within 15 minutes is measured at 37° C.

[0040] Group III: 200 μM nanoparticles concentration; 10 mM H2O2 concentration 2 o 2 3,3',5,5'-Tetramethylbenzidine (TMB) concentration is 1.2mM; Absorption spectra at 350-1000nm at three time points of 0, 5 and 10min are tested at 37°C.

[0041] The results showed that IrPcCl 2 Concentration is 200μM, when H ...

Embodiment 3

[0043] Verify the IrPcCl prepared by Example 1 2 -BSA nanoparticles catalyzed H 2 o 2 To produce the effect of oxygen-enhanced sonodynamic therapy, set the following groups respectively:

[0044] Material control group: IrPcCl 2 -BSA+ABDA, the nanoparticle concentration is 200μM, 50μLABDA (1mg / mL) solution;

[0045] ABDA control group: 50μLABDA (1mg / mL) solution;

[0046] Experimental group: IrPcCl 2 -BSA+ABDA+H 2 o 2 , the concentration of nanoparticles is 200μM, 50μLABDA (1mg / mL), H 2 o 2 The concentration is 0.5mM;

[0047] Experimental inhibition group: IrPcCl 2 -BSA+ABDA+NaN 3 , with a nanoparticle concentration of 200 μM, 50 μL of LABDA (1 mg / mL), 50 μL of saturated NaN 3 solution;

[0048] Material Inhibition Group: IrPcCl 2 -BSA+ABDA+NaN 3 , with a nanoparticle concentration of 200 mM, 50 μL of LABDA (1 mg / mL), 50 μL of saturated NaN 3 solution.

[0049] The test conditions are set as follows: occupying space: continuous, ultrasonic power: 1.5W / cm 2 ,...

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Abstract

The invention discloses application of a nano sound sensitizer to preparing optoacoustic guidance-based acoustodynamic tumor treatment drugs. The nano sound sensitizer is water-soluble nanoparticles with hydrophobic alpha-substituted iridium octabutoxy-phthalocyanine as the core and bovine serum albumin as the shell, the hydrate dynamic diameter of the nano sound sensitizer is 134.5 nm, and the Zeta surface potential of the nano sound sensitizer is -28.4 mV; the nano sound sensitizer can catalyze hydrogen peroxide to produce oxygen and convert the oxygen under ultrasonic conditions into singlet oxygen to achieve enhancement of optoacoustic guidance-based acoustodynamic treatment. When applied to preparing the optoacoustic guidance-based acoustodynamic tumor treatment drugs, the nano soundsensitizer can save external oxygen sources and achieve good effects.

Description

technical field [0001] The invention belongs to the field of medical materials, and relates to an iridium octabutoxyphthalocyanine (IrPcCl for short) substituted with a hydrophobic alpha position. 2 ) as the inner core, and it is modified with bovine serum albumin (BSA) which has good biocompatibility and is cheap and easy to obtain, and IrPcCl with excellent stability and biocompatibility is prepared 2 -BSA nanoparticles, and its use as a sound sensitizer in the preparation of photoacoustic-guided sonodynamic therapy for tumor drugs. Background technique [0002] Phthalocyanine (Phthalocyanine, Pc) is a class of porphyrin derivatives, belonging to the category of benzazepine porphyrins. Due to its 18-electron macrocyclic conjugated system, the maximum absorption of phthalocyanine is significantly red-shifted relative to that of porphyrin, so it has better photochemical properties than porphyrin. Phthalocyanine has a strong coordination ability and can coordinate with almo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K41/00A61K47/42A61P35/00
CPCA61K9/5169A61K41/0033A61P35/00
Inventor 杨红王远越高煜聪杨仕平
Owner SHANGHAI NORMAL UNIVERSITY
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