Au-agpd ternary composite asymmetric nanoparticle and preparation method and application thereof
Au-AgPd ternary composite asymmetric nanoparticles were prepared by galvanic substitution and co-reduction reactions, solving the structural symmetry problem of multi-component composite nanomaterials, realizing functional integration and spatial partitioning, and possessing efficient photothermal conversion and catalytic performance, making them suitable for combination cancer therapy.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- ZHEJIANG SCI-TECH UNIV
- Filing Date
- 2023-09-26
- Publication Date
- 2026-07-03
AI Technical Summary
Existing technologies make it difficult to prepare asymmetric structures of multi-component composite nanomaterials, resulting in uncontrollable functional integration and spatial partitioning, which affects their synergistic performance.
Au-AgPd ternary composite asymmetric nanoparticles were prepared by combining galvanic substitution reaction and co-reduction reaction with Oswald ripening effect. The selective growth of AgPd alloy at one end of gold nanoparticle bipyramidal structure was controlled by adjusting the pH of the growth solution.
The preparation of functionally diverse Au-AgPd ternary composite asymmetric nanoparticles was achieved, avoiding mutual interference between components. These nanoparticles possess highly efficient near-infrared II photothermal conversion performance and the ability to catalyze the generation of hydroxyl radicals from hydrogen peroxide, making them suitable for combined photothermal-catalytic therapy of tumors.
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Figure CN117483775B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of nanocomposite materials and their preparation, specifically to an Au-AgPd ternary composite asymmetric nano-ion, its preparation method, and its application. Background Technology
[0002] Surgery, chemotherapy, and radiotherapy are currently the three main methods of cancer treatment. However, these three traditional methods all have certain limitations, such as large incisions, slow recovery, and significant side effects. Therefore, precision medicine has become one of the current research hotspots in personalized medicine, and new cancer therapies such as phototherapy, immunotherapy, and gene therapy have emerged. Furthermore, scientists have shown that combination therapy can overcome the limitations of single-treatment approaches and achieve better therapeutic effects.
[0003] In recent years, combining nanomaterials with cancer therapy has become a trend in precision medicine. Nanomaterials possess excellent passive tumor targeting and drug delivery properties, and are expected to overcome the limitations of traditional therapies. Researchers have constructed multi-component composite nanomaterials, integrating two or more different elements into a single structural system. Due to the synergistic effect of the physical and chemical properties of different components, multi-component composite nanomaterials often exhibit richer functionality than single-component nanomaterials. They provide more possibilities for controlling, improving, and expanding the application scenarios of composite nanomaterials. For example, the combination of plasmon materials with catalytically active metals or semiconductors can generate nanostructures with novel photocatalytic properties for photothermal-catalytic combined therapy of tumors. Currently, researchers have developed a series of chemical strategies to construct multi-component nanocomposite materials, including seed-mediated methods, overgrowth methods, electrodisplacement, co-reduction, and ion exchange.
[0004] Besides the composition, the structural characteristics of composite nanomaterials themselves also strongly influence their physicochemical properties. Rational design of composite nanomaterial structures is a powerful technology for broadening their applications. Traditional multifunctional composite nanotherapeutic agents often exhibit core-shell or doped structures in their spatial distribution. In these two composite structures, the spatial positions of the components are uncontrollable and prone to mutual interference or shielding, affecting their composite performance. In contrast, multi-component asymmetric heterostructures can achieve functional integration and controllable component partitioning on the same nanoscale platform, ensuring synergistic effects while avoiding functional interference and material waste. To date, the preparation of multi-component composite asymmetric nanostructures using wet chemical synthesis methods has been extremely challenging because breaking the structural and compositional symmetry at the nanoscale in solution phase represents a breakthrough in the principle of minimum energy. Summary of the Invention
[0005] This invention addresses the limitation of existing chemical synthesis techniques, which mostly only prepare symmetrical multi-component composite nanoparticles. It provides an Au-AgPd ternary composite asymmetric nanoparticle, its preparation method, and its applications. This composite nanoparticle exhibits an asymmetric structure and diverse functions. The inventors combined galvanic substitution, co-reduction, and Oswald ripening effects to develop a novel ternary composite asymmetric nanostructure, which is then applied to integrated cancer diagnosis and treatment.
[0006] According to a first aspect of the present invention, the present invention provides a method for preparing Au-AgPd ternary composite asymmetric nanoparticles (AgPd nanodarts), comprising the following steps:
[0007] 1) Add silver nitrate to a solution of gold nanobipyramidal hexadecyltrimethylammonium chloride (CTAC), then add ascorbic acid as a reducing agent to react. Centrifuge the reaction solution to obtain gold nanobipyramidal / silver core-shell structured nanoparticles.
[0008] 2) The nanoparticles obtained in step 1) are dispersed in a cetyltrimethylammonium bromide (CTAB) solution, and then sodium hydroxide, chloropalladic acid and ascorbic acid are added in sequence. After mixing evenly, the pH of the solution is adjusted to 7.7~9.8. The reaction is allowed to stand at room temperature for more than 2 hours, and then centrifuged to obtain composite nanoparticles with gold nanobipyramidal substrate, spherical silver-palladium alloy grown at one end and the other tip exposed, namely the Au-AgPd ternary composite asymmetric nanoparticles.
[0009] As an optional embodiment of the present invention, the gold bipyramidal nanoparticles can be selected from commercially available products or prepared using methods already reported in the prior art. A preferred method for preparing the gold bipyramidal nanoparticles can be found in the literature (Sánchez-Iglesias, A.; Winckelmans, N.; Altantzis, T.; Bals, S.; Grzelczak, M.; Liz-Marzán, LM High-Yield Seeded Growth of Monodisperse Pentatwinned Gold Nanoparticles through Thermally Induced Seed Twinning. J. Am. Chem. Soc. 2017, 139, 107–110.).
[0010] As a preferred embodiment of the present invention, in step 1), the preparation process of the hexadecyltrimethylammonium chloride (CTAC) solution of gold nanoparticles is as follows: a gold nanoparticle solution with an extinction peak at 680~1000 nm and an absorbance of 2~5 is selected, centrifuged and dispersed in CTAC solution to obtain the hexadecyltrimethylammonium chloride (CTAC) solution of gold nanoparticles.
[0011] In step 1), the molar ratio of CTAC, silver nitrate, and ascorbic acid is (400~800):(3~5):(15~25); the reaction temperature is 60℃~80℃, and the reaction time is 4~8 h.
[0012] As a preferred embodiment of the present invention, in step 2), the molar ratio of CTAB, sodium hydroxide, chloropalladic acid, and ascorbic acid is (30~50):(5~7):(3~5):(3~5); the reaction temperature is room temperature, and the reaction time is 2~24 h.
[0013] As a preferred embodiment of the present invention, in step 1), the centrifugation speed is 4500-7500 rpm.
[0014] As a preferred embodiment of the present invention, in step 2), the centrifugation speed is 4000-7000 rpm.
[0015] According to a second aspect of the present invention, the present invention provides Au-AgPd ternary composite asymmetric nanoparticles prepared by the above preparation method.
[0016] As a preferred embodiment of the present invention, the support of the composite nanoparticles is a gold nanobipyramidal structure, one tip of which is coated with a spherical silver-palladium alloy, while the other tip is exposed.
[0017] As a preferred embodiment of the present invention, the plasmon resonance wavelength of the composite nanoparticles is red-shifted to the near-infrared II region, and has a near-infrared II region photothermal conversion efficiency of up to 86.7%.
[0018] According to a third aspect of the present invention, the present invention provides the application of the Au-AgPd ternary composite asymmetric nanoparticles in the catalytic generation of hydroxyl radicals from hydrogen peroxide.
[0019] According to a fourth aspect of the present invention, the present invention provides the application of the Au-AgPd ternary composite asymmetric nanoparticles in the preparation of tumor photothermal therapy drugs or tumor photothermal-catalytic combined therapy drugs.
[0020] Compared with the prior art, the present invention has the following significant advantages:
[0021] (1) The Au-AgPd ternary composite asymmetric nanoparticle prepared by this invention, which is based on gold nanobipyramidal substrate and grows AgPd alloy particles at one of the tips of the bipyramidal substrate, has not been reported before. It is an innovative structure. Compared with the core-shell structure and doped structure of traditional composite materials, this ternary composite asymmetric structure realizes the functional integration and spatial partitioning of the three components. It can achieve synergistic effect and effectively avoid mutual interference and shielding between multiple components. It has made great progress in synergistic effect.
[0022] (2) The outstanding innovation of the preparation method of ternary composite asymmetric nanoparticles in this invention is that by adjusting the pH value of the growth solution, the reaction rate is changed, thereby prompting the AgPd alloy components to migrate to one end of the gold nanoparticle bipyramid in order to meet the principle of minimum energy during the substitution reaction and co-reduction process, thus achieving selective growth at one end of the gold nanoparticle bipyramid.
[0023] (3) The Au-AgPd ternary composite asymmetric nanoparticles realized in this invention have a plasmon resonance wavelength that can be red-shifted to the near-infrared II region, and have a near-infrared II photothermal conversion efficiency of up to 86.7%. Its near-infrared II photothermal conversion performance is significantly better than most reported near-infrared II photothermal agents, making it suitable for tumor photothermal therapy.
[0024] (4) The Au-AgPd ternary composite asymmetric nanoparticles provided by the present invention have peroxidase activity and can efficiently catalyze the generation of hydroxyl radicals from hydrogen peroxide, making them suitable for tumor catalytic therapy.
[0025] (5) The present invention has low requirements for experimental instruments, the method is simple and easy to operate, and the obtained composite nanoparticles have high yield, uniform size and good dispersibility, and can be used for near-infrared II excited tumor photothermal-catalytic combined therapy. Attached Figure Description
[0026] Figure 1 Transmission electron microscopy images of (a) gold nanobipyramidal / silver core-shell structured nanoparticles and (b) Au-AgPd ternary composite asymmetric nanoparticles obtained in Example 1 of this invention.
[0027] Figure 2 This is a large-area, low-magnification transmission electron microscope image of the Au-AgPd ternary composite asymmetric nanoparticles obtained in Example 1 of the present invention.
[0028] Figure 3 This is an elemental surface scan of the Au-AgPd ternary composite asymmetric nanoparticles obtained in Example 1 of the present invention.
[0029] Figure 4The following are the extinction spectra of the Au-AgPd ternary composite asymmetric nanoparticles obtained in Example 2 of this invention: (a) the extinction spectrum and (b) the near-infrared II region illumination heating-cooling cycle curve.
[0030] Figure 5 The image shows the electron paramagnetic resonance (EPR) spectrum of the Au-AgPd ternary composite asymmetric nanoparticles obtained in Example 2 of this invention.
[0031] Figure 6 The figure shows the results of the live-death experiment on 4T1 cells using Au-AgPd ternary composite asymmetric nanoparticles obtained in Example 3 of this invention. The scale bar in the figure is 100 micrometers.
[0032] Figure 7 The image shows a transmission electron microscope (TEM) image of the product obtained in Comparative Example 1.
[0033] Figure 8 The image shows a transmission electron microscope (TEM) image of the product obtained in Comparative Example 2. Detailed Implementation
[0034] The following embodiments provide those skilled in the art with guidance on how to manufacture and evaluate the present invention. These embodiments are merely illustrative of the present disclosure and do not limit the scope of the invention. While every effort has been made to ensure accuracy regarding numerical values (e.g., quantities, temperatures, etc.), some errors and deviations should be considered. Unless otherwise stated, temperatures are expressed in °C or at ambient temperature.
[0035] Example 1
[0036] 1) Centrifuge 1 mL of a gold nanopyramidal solution with an absorbance of 3 (extinction peak at 800 nm) at 6500 rpm for 8–10 min, concentrate, and disperse in 1 mL of 0.08 M CTAC solution. Add 45 µL of 0.01 M silver nitrate solution and 22.5 µL of 0.1 M ascorbic acid solution, shake well, and incubate at 60 °C for 6 h. After centrifugation and concentration, gold nanopyramidal-silver-shelled nanoparticles are obtained. Morphological analysis of the prepared gold nanopyramidal-silver-shelled nanoparticles is shown in the appendix. Figure 1 The TEM of a nanoparticles showed that they were shaped like "rice grains".
[0037] 2) The prepared gold bipyramidal-silver shell nanoparticles were centrifuged at 6500 rpm for 8–10 min, concentrated, and dispersed in 0.004 M CTAB solution. Then, 5 µL of 0.1 M sodium hydroxide solution, 30 µL of 0.01 M chloropalladic acid solution, and 30 µL of 0.01 M ascorbic acid solution were added. The mixture was shaken well, allowed to stand at room temperature for 12 h, and centrifuged again to obtain Au-AgPd ternary composite asymmetric nanoparticles. Morphological analysis of the obtained product is shown in the appendix. Figure 1 TEM image and appendix of b Figure 2 The low-magnification TEM image shows that the obtained composite nanoparticles are dart-shaped, originating from the attached... Figure 1 TEM images of b show that only one end of the gold nanobipyramidal structure has spherical AgPd alloy growth, while the other tip remains exposed. (From the attached image...) Figure 2 Low-magnification TEM images show that the obtained composite nanoparticles are uniform in size and have a purity of over 90%. (Attached) Figure 3 This is an elemental surface scan of asymmetric nanoparticles. As can be seen from the image, the nanobipyramidal structure is composed of gold, and the spherical alloy at one end of the bipyramidal structure is composed of AgPd alloy.
[0038] Example 2
[0039] The extinction spectra of the gold nanobipyramidal particles and the prepared ternary composite asymmetric nanoparticles selected in Example 1 in the aqueous phase are shown in the appendix. Figure 4 a) As can be observed from the figure, the extinction peak of the pure gold nanobipyramid is located at 800 nm, while the extinction peak of the ternary composite asymmetric nanoparticle is at 1065 nm, confirming that growing AgPd alloy at one end of the gold nanobipyramid can cause a redshift of the extinction peak of the nanobipyramid. (1 W cm⁻¹) -2 Under 1064 nm laser irradiation, 1 mL of 100 µg mL -1 The photothermal heating-cooling cycle curve of ternary composite asymmetric nanoparticles is as follows: Figure 4 As shown in b, calculations show that the ternary composite asymmetric nanoparticles possess a near-infrared II photothermal conversion efficiency as high as 86.7%. Their near-infrared II photothermal conversion performance is significantly superior to most reported near-infrared II photothermal agents, and they exhibit strong stability, making them suitable for tumor photothermal therapy. The catalytic performance of these ternary composite asymmetric nanoparticles was detected using electron paramagnetic resonance spectroscopy (ESR). Figure 5 As shown, in the presence of hydrogen peroxide at pH 6.5, without the addition of ternary composite asymmetric nanoparticles, the ESR spectrum did not show any significant ROS signal. However, after adding the prepared ternary composite asymmetric nanoparticles to the reaction solution, the presence of •OH was clearly detected, demonstrating that the ternary composite asymmetric nanoparticles can catalyze the generation of cytotoxic hydroxyl radicals from highly expressed hydrogen peroxide in the tumor microenvironment.
[0040] Example 3
[0041] Figure 6The results show the viability of 4T1 cells in the presence and absence of light and hydrogen peroxide using the obtained Au-AgPd ternary composite asymmetric nanoparticles. The results indicate that the viability of 4T1 tumor cells did not change significantly in the presence of only the ternary composite asymmetric nanoparticles (M). However, when irradiated with a 1064 nm laser in the presence of the material, a large number of cancer cells were destroyed. Furthermore, due to the synergistic effect of the high photothermal conversion efficiency and peroxidase-like activity of the ternary composite asymmetric nanoparticles, almost complete ablation of cancer cells was observed in the material + 1064 nm laser + hydrogen peroxide group.
[0042] Comparative Example 1
[0043] The gold bipyramidal-silver shell nanoparticles obtained in step 1) of Example 1 were centrifuged at 6500 rpm for 8-10 min, concentrated, and dispersed in 0.006 M CTAC solution. Then, 5 µL of 0.1 M sodium hydroxide solution, 30 µL of 0.01 M chloropalladic acid solution, and 30 µL of 0.01 M ascorbic acid solution were added. The mixture was shaken well and allowed to stand at room temperature for 12 h. The resulting product was centrifuged, washed, and TEM samples were prepared. The morphology was observed as follows. Figure 7 As shown, the final product is a core-shell structure of gold nanoparticles with a bipyramidal core and an AgPd shell. No asymmetric ternary composite asymmetric nanoparticles were generated, proving that the CTAB solution in the growth solution in reaction step 2) cannot be replaced by the CTAC solution. Asymmetric ternary composite asymmetric nanoparticles can only be generated in the CTAB solution phase.
[0044] Comparative Example 2
[0045] The gold bipyramidal-silver shell nanoparticles prepared in step 1) of Example 1 were centrifuged at 6500 rpm for 8-10 min, concentrated, and dispersed in 0.004 M CTAB solution. Then, 10 µL of 0.1 M hydrochloric acid solution, 30 µL of 0.01 M chloropalladic acid solution, and 30 µL of 0.01 M ascorbic acid solution were added. The mixture was shaken well and allowed to stand at room temperature for 12 h. The resulting product was centrifuged, washed, and TEM samples were prepared. The morphology was observed as follows. Figure 8 As shown, the final product is a gold nanobipyramidal@AgPd fully encapsulated structure, without the formation of asymmetric ternary composite asymmetric nanoparticles. This proves that the pH of the reaction solution in the growth solution in reaction step 2) must be controlled within the range of 7.7 to 9.8. In an acidic growth solution with added hydrochloric acid, the asymmetric ternary composite asymmetric nanoparticles of this invention cannot be formed.
[0046] The above-described embodiments are merely illustrative of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. Those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.
Claims
1. A method for preparing Au-AgPd ternary composite asymmetric nanoparticles, characterized in that: Includes the following steps: 1) Silver nitrate was added to a solution of gold nanoparticles with a bipyramidal structure and hexadecyltrimethylammonium chloride, and then ascorbic acid was added as a reducing agent to carry out the reaction. The reaction solution was centrifuged to obtain gold nanoparticles with a bipyramidal@silver core-shell structure. The molar ratio of hexadecyltrimethylammonium chloride, silver nitrate and ascorbic acid was (400~800):(3~5):(15~25); the reaction temperature was 60℃~80℃ and the reaction time was 4~8 h. 2) The nanoparticles obtained in step 1) were centrifuged and dispersed in a hexadecyltrimethylammonium bromide solution, and then sodium hydroxide, chloropalladic acid, and ascorbic acid were added in sequence. After mixing evenly, the pH of the solution was adjusted to 7.7~9.
8. The molar ratio of hexadecyltrimethylammonium bromide, sodium hydroxide, chloropalladic acid, and ascorbic acid was (30~50):(5~7):(3~5):(3~5). The reaction was allowed to stand at room temperature for more than 2 hours, and then centrifuged to obtain composite nanoparticles with gold nanobipyramidal substrate, spherical silver-palladium alloy grown at one end, and the other tip exposed, namely the Au-AgPd ternary composite asymmetric nanoparticles.
2. The preparation method according to claim 1, characterized in that, In step 1), the preparation process of the hexadecyltrimethylammonium chloride solution of gold nanoparticles is as follows: a gold nanoparticle solution with an extinction peak at 680~1000 nm and an absorbance of 2~5 is selected, centrifuged and dispersed in a hexadecyltrimethylammonium chloride solution to obtain a hexadecyltrimethylammonium chloride solution of gold nanoparticles.
3. The preparation method according to claim 1, characterized in that, In step 2), the reaction temperature is room temperature and the reaction time is 2-24 h.
4. The preparation method according to claim 1, characterized in that, In step 1), the centrifugation speed is 4500-7500 rpm.
5. The preparation method according to claim 1, characterized in that, In step 2), the centrifugation speed is 4000-7000 rpm.
6. Au-AgPd ternary composite asymmetric nanoparticles prepared by the preparation method according to any one of claims 1-5.
7. The Au-AgPd ternary composite asymmetric nanoparticles according to claim 6, characterized in that, The composite nanoparticles are supported by a gold nanobipyramidal structure, with one tip of the gold nanobipyramidal structure coated with a spherical silver-palladium alloy, while the other tip is exposed.
8. The Au-AgPd ternary composite asymmetric nanoparticles according to claim 6, characterized in that, The plasmon resonance wavelength of the composite nanoparticles is red-shifted to the near-infrared II region, resulting in a near-infrared II region photothermal conversion efficiency of up to 86.7%.
9. The application of the Au-AgPd ternary composite asymmetric nanoparticles as described in claim 6 in the catalytic generation of hydroxyl radicals from hydrogen peroxide.
10. The use of the Au-AgPd ternary composite asymmetric nanoparticles according to claim 6 in the preparation of tumor photothermal therapy drugs or tumor photothermal-catalytic combined therapy drugs.