阅读说明：本技术 一种促进***效果的纳米粒子及其合成方法 (Nano particles for promoting effect of treating tumor and synthesis method thereof ) 是由 易昌凤 张宏量 于 2019-09-25 设计创作，主要内容包括：本发明提供了一种促进治疗肿瘤效果的纳米粒子及其合成方法,其合成方法包括以下步骤：将替拉扎明溶于聚乙烯醇再进行超声处理得溶液A,在冰浴条件下将羰基锰和PLGA溶于二氯甲烷并进行超声处理得溶液B,在冰浴条件下将溶液B滴入溶液A中,超声处理后得到的产物加入至聚乙烯醇溶液中,进行超声、稀释、搅拌即得最终产物。本发明使用一种全新的设计思路,合成过程中使用配合物羰基锰,合成的纳米粒子可以在肿瘤部位释放一氧化碳(CO),CO不仅能达到良好的治疗效果,还能促进肿瘤细胞有氧呼吸,消耗氧气,进而促进替拉扎明的高效使用。(The invention provides a nano particle for promoting the effect of treating tumor and a synthetic method thereof, wherein the synthetic method comprises the following steps: dissolving tirapazamine in polyvinyl alcohol, performing ultrasonic treatment to obtain a solution A, dissolving carbonyl manganese and PLGA in dichloromethane under an ice bath condition, performing ultrasonic treatment to obtain a solution B, dripping the solution B into the solution A under the ice bath condition, adding a product obtained after ultrasonic treatment into the polyvinyl alcohol solution, performing ultrasonic treatment, diluting and stirring to obtain a final product. The invention uses a brand new design idea, the complex manganese carbonyl is used in the synthesis process, the synthesized nano particles can release carbon monoxide (CO) at the tumor part, the CO not only can achieve good treatment effect, but also can promote aerobic respiration of tumor cells and oxygen consumption, and further promote the efficient use of tirapazamine.)

1. A method for synthesizing nanoparticles for promoting the effect of treating tumors is characterized by comprising the following steps:

step one, weighing 1mg of tirapazamine, dissolving the tirapazamine in 1mL of polyvinyl alcohol with the concentration of 20mg/mL, and performing ultrasonic treatment to promote dissolution to obtain a standby solution A;

weighing 20mg of manganese carbonyl and 50mg of PLGA, dissolving in 4mL of dichloromethane, and performing ultrasonic treatment under an ice bath condition to promote dissolution to obtain a standby solution B;

step three, dropwise adding the standby solution B prepared in the step two into the standby solution A prepared in the step one, and carrying out ultrasonic treatment under the ice bath condition;

step four, adding the product obtained in the step three into 12mL of PVA solution with the concentration of 50mg/mL, carrying out ultrasonic treatment, transferring the product into 100mL of deionized water, and stirring the mixture for 12 hours to obtain the final product TPZ/CO-PLGA.

2. The method for synthesizing nanoparticles for promoting tumor treatment according to claim 1, wherein the ultrasound treatment in the first step, the second step, the third step and the fourth step is performed at an ultrasound power of 400W for an ultrasound time of 60 min.

3. A nanoparticle for promoting tumor treatment effect prepared by the method of any one of claims 1-2.

Technical Field

The invention relates to the technical field of biological targeting nano-medicines, in particular to a nano-particle for promoting the effect of treating tumors and a synthesis method thereof.

Background

Tumor hypoxia is a common feature of solid tumors in humans and animals, is a powerful negative clinical biomarker, and is considered to be one of the most effective therapeutic targets in cancer therapy. On the one hand, tumor hypoxia is a major factor leading to the failure of many anticancer therapies. On the other hand, tumor hypoxia may be an attractive therapeutic target, as it underlies the major difference between tumor and normal tissues. Hypoxia-activated drugs (HAPs) are selectively highly toxic to hypoxic cells and less toxic in areas of higher oxygen tension, such as normal tissue. Thus, HAP has the potential to selectively kill hypoxic cells, thereby converting tumor hypoxia from a problem to a selective therapeutic advantage. Tirapazamine (tpz), tirapazamine, a representative HAP, exhibits up to 300-fold higher toxicity in mouse and human cancer cell lines under hypoxic conditions than aerobic conditions in vitro. As a prodrug, TPZ can be stimulated under hypoxic conditions to produce a transient oxidative radical intermediate via a one-electron reduction reaction.

Although the tumor area is an oxygen-deficient environment, it is still insufficient to activate the TPZ effect, and it is a question to decrease the oxygen concentration in the tumor area and thus improve the treatment effect of TPZ, such as the treatment scheme using PDT in combination with TPZ, where PDT is an oxygen-consuming treatment scheme that consumes part of the oxygen and thus improves the treatment effect of TPZ. In the experiment, a brand new design idea is adopted, the complex manganese carbonyl is used, carbon monoxide (CO) is released at the tumor part, the CO not only can achieve a good treatment effect, but also can promote aerobic respiration of tumor cells, consume oxygen and further promote efficient use of TPZ.

Disclosure of Invention

The invention aims to overcome the defects in the prior art, and provides a nano particle for promoting the effect of treating tumors and a synthesis method thereof, which promote aerobic respiration of tumor cells, consume oxygen, promote efficient use of tirapazamine and achieve better treatment effect.

The invention is realized by the following steps: a method for synthesizing nanoparticles for promoting the effect of treating tumors comprises the following steps:

step one, weighing 1mg of tirapazamine, dissolving the tirapazamine in 1mL of polyvinyl alcohol with the concentration of 20mg/mL, and performing ultrasonic treatment to promote dissolution to obtain a standby solution A;

weighing 20mg of manganese carbonyl and 50mg of PLGA, dissolving in 4mL of dichloromethane, and performing ultrasonic treatment under an ice bath condition to promote dissolution to obtain a standby solution B;

step three, dropwise adding the standby solution B prepared in the step two into the standby solution A prepared in the step one, and carrying out ultrasonic treatment under the ice bath condition;

step four, adding the product obtained in the step three into 12mL of PVA solution with the concentration of 50mg/mL, carrying out ultrasonic treatment, transferring the product into 100mL of deionized water, and stirring the mixture for 12 hours to obtain the final product.

Further, in the ultrasonic treatment in the first step to the fourth step, the ultrasonic power is 400W, and the ultrasonic time is 60 min.

The nano particle for promoting the effect of treating the tumor is prepared by the method.

The invention has the following beneficial effects:

the advantage of this experiment is that a new method is proposed to exacerbate the degree of hypoxia at the tumor site, thereby promoting the action of TPZ drugs. Due to the fact that the carbonyl manganese is used, due to the fact that the high hydrogen peroxide concentration in the tumor cells can promote decomposition of the carbonyl manganese to generate CO, according to relevant literature reports, the CO can promote aerobic respiration of the tumor cells, the CO can achieve the purpose of killing the tumor cells, meanwhile, the oxygen concentration in a tumor area is reduced, and conditions are provided for activation of TPZ medicines.

Drawings

FIG. 1 is an electron microscope image of the prepared nanoparticles;

FIG. 2 is the hydrated particle size of the synthesized microspheres;

FIG. 3 is a graph of the activity of tumor cells under the action of three types of particles, the x-axis representing the concentration of manganese carbonyls and tirapazamine, and the y-axis representing the survival rate of tumor cells;

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.