CN110585214A

CN110585214A - Nano particles for promoting effect of treating tumor and synthesis method thereof

Info

Publication number: CN110585214A
Application number: CN201910911910.8A
Authority: CN
Inventors: 易昌凤; 张宏量
Original assignee: Hubei University
Current assignee: Hubei University
Priority date: 2019-09-25
Filing date: 2019-09-25
Publication date: 2019-12-20

Abstract

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.

Description

Nano particles for promoting effect of treating tumor and synthesis method thereof

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.

Example 1

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

The nanoparticle TPZ/CO-PLGA for promoting the effect of treating the tumor is prepared by the method.

Example 2

The shape and structure of the prepared nano particles are researched:

the nanoparticles were observed to have a spherical structure around 100nm under a transmission electron microscope, see fig. 1.

Example 3

By studying the hydrated particle size of the nanoparticle, see fig. 2, it is known that the hydrated particle size of the PLGA microsphere synthesized by the present invention is about 110 nm.

Example 4

The change of the survival rate of the tumor cells under the action of the three particles is researched. It can be seen from figure 3 that the best therapeutic effect is achieved when CO is combined with TPZ. Indicating that CO has an interaction promoting effect with TPZ.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.

Claims

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

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.