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Targeted oxygen-carrying nano sonosensitizer and preparation method thereof

A sonosensitizer and oxygen-carrying technology, applied in the field of nanomedicine, can solve the problems of inability to achieve sonodynamic therapy and inability to carry oxygen, and achieve the effects of reducing phototoxicity, improving safety, and improving bioavailability

Pending Publication Date: 2021-01-26
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Nanoparticles of manganese porphyrin sonosensitizers coated with human serum albumin have also been reported in the prior art, but they cannot carry oxygen efficiently, so efficient sonodynamic therapy cannot be achieved.

Method used

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  • Targeted oxygen-carrying nano sonosensitizer and preparation method thereof
  • Targeted oxygen-carrying nano sonosensitizer and preparation method thereof
  • Targeted oxygen-carrying nano sonosensitizer and preparation method thereof

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preparation example Construction

[0046] The preparation method of the targeted oxygen-carrying nano sonosensitizer of the present invention is prepared by a one-step ultrasonic method. With the volatilization of the chloroform solvent, the hydrophobic manganese porphyrin is wrapped in the hybrid protein body to form a spherical targeted oxygen-carrying nano Sound sensitizer. Specific steps are as follows:

[0047] (1) Preparation of manganese porphyrin

[0048] ①Macrocyclic compound of porphyrin structure (such as 5,10,15,20-tetrakis(4-carboxyphenyl) porphyrin, PP) in equimolar ratio, and metal manganese salt (manganese chloride, manganese sulfate or acetic acid Manganese at least one) mixed, under inert gas protection, stirring, heating to reflux, reaction stopped, cooled to room temperature;

[0049] ②The precipitate was filtered, washed with deionized water, and dried in vacuum. Separation by column chromatography, low-temperature rotary evaporation, drying, and collecting samples to obtain manganese po...

Embodiment 1

[0055] Embodiment 1 The preparation method of targeted oxygen-carrying nano-sound sensitizer

[0056] Specifically include the following steps:

[0057] (1) Preparation of manganese porphyrin

[0058] ① 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (PP) in equimolar ratio, purchased from Bailingwei Technology Co., Ltd., mixed with manganese chloride in anhydrous DMF solution, under nitrogen protection Under stirring, heating and reflux for 2 hours, UV-Vis absorption spectrometer monitors the progress of the reaction. After the reaction solution changes from black red to grass green, and the Q band peaks change from 4 to 2 with a certain degree of red shift, the reaction Stop and cool to room temperature;

[0059] ②The precipitate was filtered, washed with deionized water, and dried in vacuum. Then use column chromatography to separate and purify using silica gel as the stationary phase and dichloromethane and methanol at a volume ratio of 3:1 as the mobile phase. Rotary ev...

Embodiment 2

[0066] Embodiment 2 The preparation method of targeted oxygen-carrying nano-sound sensitizer

[0067] In this example, the ratio of human serum albumin to oxygen-carrying hemoglobin, the pH value of the system, and the time of ultrasound are different from those in Example 1. The pH value directly affects the particle size of the oxygen-carrying nano-sensitizer, and the particle size directly determines The enrichment amount of the oxygen-carrying nano-sound sensitizer at the tumor site was determined. The ultrasonic time directly affects the particle size of the oxygen-carrying nano sonosensitizer, and the ratio of human serum albumin to oxygen-carrying hemoglobin will also affect the particle size.

[0068] Specifically include the following steps:

[0069] (1) Preparation of manganese porphyrin

[0070] ①Mix 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (PP) and manganese acetate in anhydrous DMF solution in equimolar ratio, stir and heat to reflux for 6h under argon prot...

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Abstract

The invention discloses a targeted oxygen-carrying nano sonosensitizer and a preparation method thereof, and the targeted oxygen-carrying nano sonosensitizer is prepared by hybridizing human serum albumin (HSA) and oxygen-carrying hemoglobin (Hb) by an ultrasonic method and wrapping hydrophobic sonosensitizer manganese porphyrin (MnPP). The method is simple in preparation process, and the preparedtargeted oxygen-carrying nano sonosensitizer is stable in property, high in bioavailability and good in targeting property, and can efficiently deliver exogenous oxygen molecules and MnPP into tumorsin a targeting manner, so that the tumor anoxic microenvironment is improved, and the sonodynamic curative effect is improved.

Description

technical field [0001] The invention relates to the field of nanomedicine, in particular to a targeted oxygen-carrying nano-sound sensitizer and a preparation method thereof. Background technique [0002] In the prior art, tumor phototherapy has gradually become a research hotspot in cancer treatment due to its advantages of non-invasiveness and spatiotemporal control. Tumor phototherapy mainly includes photodynamic therapy (PDT) and photothermal therapy (PTT). However, the tissue penetration depth of near-infrared light is limited, and the treatment effect of deep tumors is not good. In contrast, sonodynamic therapy (SDT) has attracted widespread attention, using the stronger tissue penetration ability of ultrasound to make the sonosensitizers accumulated in deep tumors generate reactive oxygen species (ROS) or cavitation effects to Treat tumors. At present, sonodynamic therapy has been used clinically, and 3 patients with advanced breast cancer have been successfully cu...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/51A61K47/42A61P35/00
CPCA61K41/0033A61K9/5169A61P35/00
Inventor 蔡林涛尹婷邢婕华马爱青郑明彬陈泽
Owner SHENZHEN INST OF ADVANCED TECH
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