A Pt@Ag platinum-silver nano alloy and preparation method thereof

Abstract

A Pt@Ag platinum-silver nanoalloy and its preparation method are disclosed, specifically comprising: preparing small-diameter platinum nanoseeds using sodium borohydride as a reducing agent; preparing larger-diameter platinum nanoparticles using ascorbic acid as a reducing agent; and constructing a core-shell platinum-silver nanoalloy (Pt@Ag) using the larger-diameter platinum nanoparticles as templates. The internal fine structure, morphology, and optical properties of the prepared platinum-silver nanoalloy are characterized using transmission electron microscopy and ultraviolet absorption spectroscopy. This invention modifies and improves upon previous methods for preparing gold-silver core-shell nanoalloys, exploring a novel preparation technique for platinum-silver nanoalloys. The platinum-silver nanoalloy prepared by this invention is based on nanochemical preparation technology, and its synthesis method is simple, low-cost, and exhibits good biocompatibility, showing promise as a potent nano-radiosensitizing material in the radiotherapy of malignant tumors.

Description

Technical Field

[0001] The invention relates to the field of chemical synthesis nano material preparation, and in particular to a Pt@Ag platinum-silver nano alloy and a preparation method thereof. Background Art

[0002] According to the latest global cancer burden data released by the World Health Organization's International Agency for Research on Cancer, there were 19.29 million new cancer cases and 9.96 million deaths worldwide last year. The top ten cancers are: breast cancer, lung cancer, colorectal cancer, prostate cancer, gastric cancer, liver cancer, cervical cancer, esophageal cancer, thyroid cancer, and bladder cancer. Among them, due to China's large population base, there are 4.57 million new cancer cases in China, accounting for 23.7% of the world's total, and 3 million cancer deaths, accounting for 30% of the world's total, ranking first in the world in terms of quantity. Cancer has become a potential threat to people's health, seriously affecting the health level of the people. At present, traditional tumor treatments mainly include surgical treatment, chemotherapy, radiotherapy, etc., and each treatment method has its own advantages and disadvantages.

[0003] Ionizing radiation therapy that relies on high-energy radiation, i.e. radiotherapy, plays an important role in the treatment of early and late stage cancer. However, the dose of radiotherapy cannot be increased indefinitely because it has side effects on normal tissues, and radiotherapy is a local treatment. Once the cancer metastasis occurs, radiotherapy will lose its effect. At the same time, most malignant tumor cells have poor sensitivity to radiation, resulting in poor radiotherapy effect. The radiosensitivity of tumor cells is also related to many factors such as tumor cell type, degree of cell differentiation, cell cycle, etc. In order to improve the efficacy of radiotherapy, although radiosensitizers have achieved certain results in clinical practice, their application in radiotherapy is still limited because hypoxic cancer cells are in a hypoxic state. For different cancers, the development of more and more new radiosensitizers has become the pursuit of medical workers.

[0004] In recent years, with the development of nanoscience and technology, metal nanoparticles have unique physical and chemical properties and strong attenuation of X-rays. A large number of metal nanomaterials are expected to be used as a new radiosensitizer for tumor radiotherapy, such as gold, platinum, silver, bismuth, tungsten, tantalum, hafnium, molybdenum, iron, gadolinium and cerium. In the simulation calculation of nanomaterial radiosensitization, some researchers used Monte Carlo calculation tools to compare the electron scattering, excitation and dose deposition in high atomic number metal nanoparticles such as platinum, gold, silver and iron, and believed that platinum and gold are the best nanoradiosensitizers, followed by silver and gadolinium. Generally speaking, metal nanosensitizers have the following advantages: (1) good biocompatibility, and can achieve enhanced therapeutic effects at a lower radiotherapy dose; (2) stable chemical properties, not easy to react with other substances; (3) can achieve enhanced penetration and retention effect in tumor tissue, and can be enriched for a long time, with a suitably long biological half-life, and effective within the commonly used radiotherapy fractionated dose; (4) have a strong sensitization effect on hypoxic tumor cells in the proliferation phase. Therefore, how to design and synthesize a series of metal radiosensitizers with excellent sensitization properties and try to use them in cancer radiotherapy research has become a top priority in basic research.

[0005] At present, most of the research on metal radiosensitizers is focused on gold nanomaterials, and relatively few studies are conducted on other metal materials. In order to introduce the advantages of nanomaterials into the field of nano-tumor therapy, it is urgent to develop many new types of simple or composite metal nanosensitizers for the field of nano-tumor therapy. Summary of the invention

[0006] Based on the radiosensitization properties of platinum and silver, the present invention attempts a method for preparing platinum-silver nanoalloy particles, characterizes and analyzes their structure and optical properties, and provides guidance for the development of new metal radiosensitizers. This composite metal nanoalloy takes into account the sensitization properties of both platinum and silver and has good biocompatibility, which will play a synergistic role in the field of tumor radiotherapy.

[0007] Specifically, the present invention provides a Pt@Ag platinum-silver nano alloy and a preparation method thereof, comprising the following steps:

[0008] S1: Preparation of platinum nanoparticles by reducing chloroplatinic acid with sodium borohydride;

[0009] S2: Using platinum seeds as templates, ascorbic acid was used to reduce chloroplatinic acid to prepare platinum (Pt) nanoparticles with larger particle sizes;

[0010] S3: Using platinum nanoparticles as templates, ascorbic acid was used to reduce silver nitrate to prepare platinum-silver nanoalloy (Pt@Ag);

[0011] Furthermore, the step S1 specifically includes:

[0012] Take 0.688mL of freshly prepared 1% chloroplatinic acid, add 43mL of boiling water, keep boiling, after 1 minute, add 1.1mL of mixed solution (1% sodium citrate and 0.05% citric acid), half a minute later, quickly add 5.5mL of freshly prepared 0.08% sodium borohydride (containing 1% sodium citrate and 0.05% citric acid), after 10 minutes, cool to room temperature to obtain platinum nano seeds. The dispersion should be used immediately and should not be stored for a long time.

[0013] Furthermore, the step S2 specifically includes: adding 28 mL of deionized water, 0.36 mL of 1% chloroplatinic acid, and then adding 0.35 mL of 25% citric acid and 0.5 mL of 1.25% ascorbic acid (containing 1% sodium citrate) to 1 mL of the newly prepared platinum nanoseed dispersion, maintaining vigorous stirring, slowly heating to boiling, and maintaining the reaction for half an hour. After that, the mixed solution is centrifuged, washed twice with water, and dispersed in 20 mL of 0.5% sodium citrate, and refrigerated at 4° C. for use, to obtain a platinum nanoparticle dispersion.

[0014] Furthermore, the step S3 specifically includes: taking 20 mL of ultrapure water, adding 0.2 mL of 9 mg / mL hexadecyltrimethylammonium bromide aqueous solution, 1 mL of 17.6 mg / mL ascorbic acid solution, 0.034 mL of 1% silver nitrate solution, and 1 mL of platinum nanoparticle dispersion in sequence, maintaining gentle stirring, and then adding 0.1 mL of 1 mol / L sodium hydroxide dropwise, maintaining room temperature of 25° C. for 10 minutes to obtain Pt@Ag platinum-silver alloy nanoparticles.

[0015] Furthermore, the average particle size of the platinum nanoseeds prepared in step S2 is about 4.5 nm.

[0016] Furthermore, the average particle size of the larger platinum nanoparticles prepared in step S3 is about 15 nm.

[0017] Furthermore, in step S4, the reaction is strictly controlled to be carried out at room temperature of 25° C., and the indoor ambient temperature needs to be strictly controlled in winter.

[0018] The present invention also provides a Pt@Ag platinum-silver nano alloy with a core-shell structure prepared by the above preparation method.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) The platinum nanoparticles of the present invention are prepared by a two-step method, using a small-particle-size platinum seed of 4.5 nm as a template to synthesize platinum nanoparticles with a larger particle size of 15 nm. The platinum nanoparticles prepared by this synthesis method have the advantages of uniform particle size, good stability, and easy control.

[0021] (2) The preparation process of platinum nanoparticles and platinum-silver nanoalloys uses ascorbic acid as a reducing agent, which has the advantages of low cost, mild reaction conditions, simple synthesis method and easy operation.

[0022] (3) Compared with pure platinum nanoparticles, platinum-silver nanoalloys combine the dual properties of metal platinum and silver, and will have greater application potential in enhancing the sensitivity and efficacy of tumor radiotherapy. In addition, the average particle size of the prepared platinum-silver nanoalloy is about 30nm, which has an enhanced penetration and retention effect in the cancerous site in the blood circulation in the body.

[0023] (4) The platinum-silver nanoalloy and its preparation method proposed in the present invention can be used as a research and development platform for new composite metal nanosensitizers. By designing and synthesizing different metal nanoalloys, the synergistic effect between the metal elements can be utilized to achieve the purpose of enhancing the radiation sensitization effect, providing a guiding idea for the development of new metal nanosensitizers. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Transmission electron microscopy (TEM) images of small-size Pt nanoseeds;

[0025] Figure 2 Transmission electron microscopy (TEM) images of Pt nanoparticles with larger particle sizes;

[0026] Figure 3 It is the ultraviolet absorption spectrum (UV-vis) of Pt nanoparticles with larger particle size;

[0027] Figure 4 Transmission electron microscopy images of Pt@Ag nanoparticles and their internal microstructure;

[0028] Figure 5 This is the UV absorption spectrum of Pt@Ag nanoalloy. DETAILED DESCRIPTION

[0029] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical methods in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0030] Example

[0031] Example 1

[0032] Preparation of platinum nanoseeds: Sodium borohydride reduction method was used. Specifically, 0.688 mL of newly prepared 1% chloroplatinic acid was added to 43 mL of boiling water, and kept boiling. After 1 minute, 1.1 mL of mixed solution (1% sodium citrate and 0.05% citric acid) was added. After half a minute, 5.5 mL of newly prepared 0.08% sodium borohydride (containing 1% sodium citrate and 0.05% citric acid) was quickly added. After 10 minutes, the solution was cooled to room temperature to obtain platinum nanoseeds. The transmission electron microscope effect is shown in the figure below. Figure 1 As shown in the figure, the average particle size of the prepared platinum nanoseeds under microscopic observation is about 4.5nm, and they are nearly spherical particles with uniform particle size and good dispersibility. In particular, the prepared platinum nanoseed dispersion needs to be used immediately and is not suitable for long-term storage.

[0033] Example 2

[0034] The small-sized platinum nano seeds prepared in Example 1 were used as templates, and chloroplatinic acid was reduced by ascorbic acid to prepare platinum (Pt) nanoparticles with larger particle sizes. Specifically, 1 mL of the newly prepared platinum nano seed dispersion was added with 28 mL of deionized water, 0.36 mL of 1% chloroplatinic acid, and then 0.35 mL of 25% citric acid and 0.5 mL of 1.25% ascorbic acid (containing 1% sodium citrate) were added in sequence, and vigorous stirring was maintained, and the mixture was slowly heated to boiling. After the reaction was maintained for half an hour, the mixed solution was centrifuged, washed twice with water, and dispersed in 20 mL of 0.5% sodium citrate, and refrigerated at 4°C for standby use, to obtain a platinum nanoparticle dispersion, the transmission electron microscope image of which is shown in FIG. Figure 2 As shown, under microscopic observation, the average particle size of the prepared Pt nanoparticles is about 15 nm, the particle size is uniform, the dispersion is good and the stability is strong, and it presents a monodisperse nanoflower structure with a rough surface and a large specific surface area. Figure 3 The figure shows the ultraviolet absorption spectrum (UV-vis) of the prepared Pt nanoparticles. It can be seen from the spectrum that it has a maximum characteristic absorption peak at 295nm.

[0035] Example 3

[0036] Based on the previous ideas of preparing gold-silver core-shell nanoalloys, the platinum-silver nanoalloy (Pt@Ag) was prepared by modifying and improving the larger-sized platinum nanoparticles prepared in Example 2 as a template and using ascorbic acid to reduce silver nitrate. Specifically, take 20 mL of ultrapure water, add 0.2 mL of 9 mg / mL hexadecyltrimethylammonium bromide aqueous solution, 1 mL of 17.6 mg / mL ascorbic acid solution, 0.034 mL of 1% nitrate solution, and 1 mL of platinum nanoparticles in sequence, keep stirring gently, and then add 0.1 mL of 1 mol / L sodium hydroxide dropwise, keep the room temperature at 25°C for 10 minutes, and the prepared platinum-silver alloy (Pt@Ag) nanoparticles are obtained. The preparation process must be strictly controlled to react at room temperature of 25°C. Figure 4 As shown in the transmission electron microscope picture, the prepared platinum-silver nanoalloy has a core-shell structure, but unlike the typical core-shell structure of gold-silver alloy, the structural distribution of nanosilver and platinum nanoparticles is relatively complex, with some platinum nanoparticles completely distributed in the center of the nanosilver, and some distributed at one end of the silver nanostructure, and the shape of the nanosilver is relatively irregular, presenting a spherical or rod-like morphology. In particular, compared with the simple platinum nanoparticles prepared in Example 2, although clear platinum nanoparticles can still be seen in the platinum-silver nanoalloy, the edge flower-like structure of the platinum nanoparticles is relatively inconspicuous, and there is a tendency to ablate slightly. Statistical data show that the average particle size of the prepared platinum-silver nanoalloy is about 30nm, and this particle size range is conducive to the long-term retention of nanoparticles in the blood circulation in the body and the enhanced penetration effect. Figure 5 The figure shows the ultraviolet absorption spectrum of platinum-silver nanoalloy. It can be seen that the prepared Pt@Ag nanoparticles have the largest characteristic absorption peak only at 414nm, which is mainly derived from the characteristic absorption peak of the silver nanoparticle shell.

Claims

1. A method for preparing Pt@Ag platinum-silver nanoalloy, characterized in that: The following steps are involved: S1: Preparation of platinum nanoseeds by reducing chloroplatinic acid with sodium borohydride; S2: Using platinum nanoseeds as templates, ascorbic acid was used to reduce chloroplatinic acid to prepare platinum nanoparticles with larger particle sizes. The average particle size of the platinum nanoparticles was 15 nm. S3: Using platinum nanoparticles as templates, ascorbic acid was used to reduce silver nitrate to prepare Pt@Ag platinum-silver nanoalloy; Step S1 specifically comprises: adding a newly prepared 1% chloroplatinic acid solution into a certain amount of boiling water, keeping the water in a boiling state for one minute, adding the mixed solution, and after half a minute, quickly adding the newly prepared sodium borohydride, reacting for a period of time, and cooling to room temperature to obtain platinum nano seeds; Step S2 specifically comprises: adding a certain amount of newly prepared platinum nano seed dispersion to deionized water, followed by adding 1% chloroplatinic acid, and then adding 25% citric acid and 1.25% ascorbic acid in sequence, maintaining vigorous stirring, slowly heating to boiling, maintaining the reaction for a period of time, centrifuging the mixed solution, washing it twice, and dispersing it in 0.5% sodium citrate, and refrigerating it for later use, thereby obtaining a platinum nano particle dispersion; Step S3 specifically includes: adding 9 mg / mL of hexadecyltrimethylammonium bromide (CTAB) aqueous solution, 17.6 mg / mL of ascorbic acid solution, 1% of silver nitrate solution, and platinum nanoparticles in ultrapure water in sequence, maintaining gentle stirring, and then adding 1 mol / L of sodium hydroxide dropwise, maintaining room temperature for a certain period of time to react, thereby obtaining Pt@Ag platinum-silver nanoalloy particles.

2. The preparation method according to claim 1, characterized in that The average particle size of the platinum nanoseeds is 4.5 nm.

3. The preparation method according to claim 1, characterized in that: In the step S3, the reaction is carried out at room temperature of 25°C.

4. Pt@Ag platinum-silver nanoalloy prepared by the preparation method described in any one of the above claims.

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