Multicolor Luminescent Gold Nanoclusters: From Structure to Biosensing and Bioimaging

Yafang Sun; Ziping Zhou; Tong Shu; Lisheng Qian; Lei Su; Xueji Zhang

doi:10.7536/PC200637

Progress in Chemistry ›› 2021, Vol. 33 ›› Issue (2) : 179-187 DOI: 10.7536/PC200637

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Multicolor Luminescent Gold Nanoclusters: From Structure to Biosensing and Bioimaging

Yafang Sun ¹^,²
, Ziping Zhou ¹^,²
, Tong Shu ¹^,²^,³^,^*
, Lisheng Qian ¹^,^*
, Lei Su ¹^,²
, Xueji Zhang ¹^,²^,⁴^,^*

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Abstract

Gold nanoclusters are a new kind of "Quasi-molecule" nanomaterials with luminescent properties. By controlling the number of gold atoms and the composition of ligands, gold nanoclusters can realize the emission of different bands under the same excitation, thus showing the "colorful" luminescence characteristics, which make them widely used in many fields such as photocatalysis, optical devices, sensing, and imaging. Therefore, the development and optimization of the synthesis method of gold nanoclusters with good fluorescence performance have been a research hotspot in the field of chemical biomaterials. In this paper, based on the luminescent color of gold nanoclusters, the synthesis principles and methods of corresponding gold nanoclusters are summarized according to different colors, and the factors affecting the luminescent properties of gold nanoclusters are explored. At the same time, the applications of these "colorful" gold nanoclusters in biosensing and bioimaging in recent years are summarized, and the challenges and development trends of gold nanoclusters are discussed and prospected respectively.

Contents

1 Introduction

2 Blue and green luminescent gold nanoclusters

2.1 Synthesis

2.2 Application

3 Yellow,orange and red luminescent gold nanoclusters

3.1 Synthesis

3.2 Application

4 Near-infrared gold nanoclusters

4.1 Synthesis

4.2 Application

5 Conclusion and outlook

Graphical abstract

Keywords

gold nanoclusters / luminescence / ligands / biosensing / bioimaging

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Yafang Sun, Ziping Zhou, Tong Shu, Lisheng Qian, Lei Su, Xueji Zhang. Multicolor Luminescent Gold Nanoclusters: From Structure to Biosensing and Bioimaging. Progress in Chemistry, 2021, 33(2): 179-187 DOI:10.7536/PC200637

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1 Introduction

Gold nanocluster is a kind of luminescent material with a particle size of about 2 nm. Due to the quantum confinement effect, this kind of material has special "molecular formula" optical properties. In addition, gold nanoclusters have the advantages of small size, multi-band luminescence, high catalytic performance and low biological toxicity, which can be attributed to its volume effect, surface effect, quantum size effect and biological mildness^[1⇓~3]^[4]. As the outstanding advantage of gold nanoclusters, excellent luminescence properties have been widely concerned by researchers, and to some extent determine that gold nanoclusters can be applied in many biochemical fields^[5⇓⇓~8]. Gold nanoclusters have become a hot topic in the field of research because of their good properties and wide applications^[9].

There are two methods to synthesize gold nanoclusters: top-down etching method and bottom-up template method. The preparation of gold nanoclusters by template method refers to the use of reducing substances to reduce Au³⁺ to Au⁺ and Au, and then combine with reducing substances or ligand molecules to form luminescent nanoscale gold clusters. Template method has become a common method for the synthesis of gold nanoclusters because of its simplicity and convenience^[10⇓~12]. Etching method and template method adopt completely different synthesis strategies. Etching method uses etchant to gradually strip atoms or directly split them, so that large-sized materials can be reduced to small-sized nanoclusters that can emit light. One of the advantages of the etching method is that unstable gold nanoclusters can be transformed into gold nanoclusters with uniform size and high thermal stability by controlling the kinetic reaction conditions, which is called "size focusing"^[13,14]. On the basis of these two kinds of synthetic methods, many new synthetic methods have been derived by changing the synthetic conditions. Gold nanoclusters with different ligands, different numbers of gold atoms and different spatial structures can be synthesized by using different synthesis methods or controlling different synthesis conditions, in which the number of gold atoms and the nature of ligands are two important factors affecting the luminescent properties of gold nanoclusters^[15]^[16⇓~18]. These gold nanoclusters with different luminescence properties have good applications in biosensing and biological imaging^{[19⇓⇓~22]}. Therefore, it is particularly important to control the luminescent properties of the products by exploring the relationship between various methods and structures, which has always been a difficult point in research. At the same time, how to optimize the synthesis route and efficiently synthesize gold nanoclusters has also been the focus of attention of scholars.

In this paper, we classify the gold nanoclusters into three categories according to the luminescent color, namely, blue-green cool color, yellow-orange-red warm color and near-infrared gold nanoclusters. On the basis of color classification, the effects of pH, temperature, ultrasound and microwave on the luminescent properties of gold nanoclusters were explored, and it was pointed out that the number of gold atoms and the nature of ligands could affect the luminescent properties of gold nanoclusters. Based on the color classification, the wide applications of gold nanoclusters in biosensing and bioimaging by means of various excitation wavelengths are summarized.

2 Blue-green luminescent gold nanocluster

2.1 Synthesize

For the blue-green luminescent gold nanoclusters, the luminescent color of the gold nanoclusters directly depends on the number of gold atoms contained in the clusters. Blue-emitting gold nanoclusters generally contain less than 10 gold atoms and have an emission wavelength of 400-495 nm, and can be synthesized by a bottom-up template method. A variety of templates were used, and Au₈ blue-emitting gold nanoclusters were successfully synthesized by using the first synthesized dendrimer, polyamidoamine dendrimer (PAMAM) as the template^[23]. The green-emitting gold nanoclusters have more than 10 gold atoms as the core, and the emission wavelength is 495 ~ 550 nm. Li et al. Synthesized a green-emitting gold nanocluster at 502 nm with mercaptocyclodextrin as the ligand, and the gold nanocluster contains about 11 gold atoms^[24]. The steric hindrance and structure of the template can effectively control the number of gold atoms in the gold nanoclusters, and the luminescent color of the gold nanoclusters mainly depends on the number of gold atoms.

The blue luminescent gold nanoclusters contain a small number of gold atoms, have relatively simple structures and narrow size ranges, and the synthesis efficiency can be improved by synthesizing products with concentrated sizes. The photoluminescent properties and size concentration of gold nanoclusters can be improved by using the etching synthesis method with auxiliary conditions, which is helpful to improve the synthesis efficiency. Zhou et al. Synthesized Au₈ with high luminescence intensity by ultrasonic treatment in water to accelerate the etching of gold nanocrystals by biomolecules such as double-stranded DNA. The addition of ultrasonic conditions made the surface atoms of gold nanocrystals rearrange actively.And finally, a lay of stable chemical bonds is for on that surface of the gold nanocluster, so that the stability and the luminescent performance of the gold nanocluster are improved^[25]. Lu et al. Found that hydrogen peroxide can be used as a catalyst to promote the etching of gold nanoparticles by ligands with polyethyleneimine as a protective agent. The catalytic reaction can produce a blue-emitting Au₈ with a quantum yield of 28.8%. The use of hydrogen peroxide greatly improves the size concentration of the synthesized gold nanoclusters, thus achieving size focusing to a greater extent^[26].

In the synthesis process of the blue-green luminescent gold nanoclusters, the luminescent color of the nanoclusters can be controlled by changing the synthesis conditions. For example, the same template can be used to synthesize gold nanoclusters with different atomic numbers by changing the conditions, and the different atomic numbers will cause the gold nanoclusters to emit different colors of light. As an important and controllable reaction condition in synthesis, pH is often changed to regulate the structure of gold nanoclusters. Kawasaki et al. Found that the number of gold atoms in gold nanoclusters synthesized with porcine protease as a template varies with the pH of the synthesis (as shown in fig. 1A)^[27]. This is because the amino acid composition of porcine protease is rich, and different amino acids can carry different charges by changing the pH value, so that the template has different degrees of reducibility and diversified spatial structures, thereby synthesizing the blue-emitting Au₈ and the green-emitting Au₁₃.

By changing the properties of the template or the ligand, the luminescence intensity of the gold nanocluster can be controlled on the basis of not changing the number of gold atoms. When DNA is used as a template to synthesize gold nanoclusters, the DNA sequence has a close relationship with the luminescence intensity of the synthesized gold nanoclusters. Kennedy et al. Found that blue fluorescent gold nanoclusters can be prepared by using artificially synthesized polycytosine (C₃₀)DNA as a template under weak acid conditions and polyadenine (A₃₀)DNA as a template under neutral conditions,The experimental phenomenon showed that the luminescence intensity of gold nanoclusters synthesized with different sequences of DNA as templates was different, and later studies also confirmed that higher cytosine content would lead to better luminescence performance of the products^[28]. This may be related to the covalent interaction between nitrogen and oxygen atoms and gold atoms in DNA bases and non-covalent interaction such as hydrogen bonding.

Deng et al synthesized gold nanoclusters emitting green light by using 6-aza-2-thiothymine (ATT) as a ligand, and found that the introduction of L-arginine could regulate the state of the ligand molecule, thereby affecting the intensity of the green luminescence of the gold nanoclusters^[29]. The guanidino group of L-arginine is tightly bound to the ATT shell of the gold nanocluster, and this binding can reduce the non-radiative relaxation of the excited state by inhibiting the intramolecular vibration and rotation of ATT, thus resulting in enhanced luminescence (as shown in fig. 1b).

2.2 Application

Blue-green light has short wavelength and short propagation distance, and the blue-emitting gold nanoclusters are mostly applied to the detection of substances in the field of biosensing by changing the luminescent signal. When used for detection, the ligands of gold nanoclusters are usually functionalized, or the sensing design is based on the properties of the template itself. Luo et al. Synthesized a Au₈ with blue luminescence by using a synthetic polypeptide (KTEEISEVNLDAEFRHDSGY sequence) as a template, and found that the luminescence intensity of the gold nanocluster was inversely proportional to the length of the template polypeptide under certain conditions, which was related to the smaller size of the gold nanocluster formed by a shorter polypeptide chain. By using this characteristic, the activity of BACE1 hydrolase could be detected^[30]. During detection, the BACE1 hydrolase can hydrolyze the polypeptide template of the gold nanocluster, so that the luminescence signal is changed to achieve the purpose of sensing.

Green light, as a human eye sensitive light, has a wide range of applications in the field of biological sensing, and also has a certain application in the field of biological imaging. The green luminescent gold nanoclusters synthesized by Li et al. Can specifically recognize and capture carcinogen 4-nitrophenol (4-NP), and then the complex formed by gold nanoclusters and 4-NP can quench its luminescence due to Internal Filtering Effect (IFE).Due to this characteristic, the gold nanoclusters have been applied to the detection of 4-NP^[24]. Deng et al. Found that the synthesized green luminescent gold nanoclusters can be used to detect the activity of arginase, and the detection principle is that the hydrolysis of the enzyme to the template can cause the shell structure of the gold nanoclusters to change and then cause the luminescence to decrease.It was found that this kind of sensing is highly feasible (as shown in fig. 2, a, B and C are the luminescence intensities of gold nanoclusters stabilized by ligands, gold nanoclusters added with L-arginine and gold nanoclusters added with L-arginine and arginase, respectively)^[31]. Wei et al designed and synthesized gold nanoclusters with green luminescence at 516 nm, which can be used in cell imaging^[32].

3 Yellow orange-red luminescent gold nanocluster

3.1 Synthesize

The emission wavelengths of the gold nanoclusters emitting yellow-orange-red light are 530 ~ 560 nm, 560 ~ 610 nm and 610 ~ 760 nm, respectively. The size of this kind of gold nanoclusters is between the blue-green luminescent and near-infrared luminescent gold nanoclusters, which can be synthesized by a simple template method. Deng et al. Synthesized gold nanoclusters with yellow luminescence at 530 nm using methionine as a template^[33]. Using DL-homocysteine as a template, Xu et al synthesized gold nanoclusters with orange luminescence at 560 nm^[34]. Xie et al. Proposed a classical synthesis method of red luminescent gold nanoclusters: under alkaline conditions at 37 ℃, based on the strong reducibility of tyrosine in Bovine serum protein (BSA) and the protection of sulfur in cysteine, red luminescent gold nanoclusters with quantum yield of about 6% were synthesized^[35]. Microwave-assisted method has certain advantages in improving the efficiency of template synthesis. Microwave-assisted synthesis usually shortens the reaction time by heating to improve the synthesis efficiency, and some research teams have shortened the synthesis time from tens of hours to several minutes by means of microwave-assisted synthesis.Gold nanoclusters with strong red luminescence were prepared by using bovine serum albumin (BSA) and human serum albumin (HSA) as templates, which provided a more efficient way for the subsequent synthesis^[36].

In the yellow-orange-red luminescent gold nanoclusters, the luminescent color also depends on the number of gold atoms in the gold nanoclusters, which is embodied by the different luminescent colors of gold nanoclusters with different sizes. Bain et al. synthesized Au₁₂(1.7 nm) emitting orange light at 590 nm, smaller gold nanoclusters emitting yellow light at 545 nm (1.7-1.4 nm) and green light at 510 nm (size 1.4 nm) by ligand exchange and top-down etching (as shown in Figure 3A).The decrease in the size of gold nanoclusters directly corresponds to the decrease in the number of core gold atoms, and the difference in etching time during synthesis determines the number of core atoms of gold nanoclusters, which also directly affects the emission wavelength of gold nanocluster (as shown in Fig. 3B)^[37]. This shows that the luminescence color is strongly dependent on the size of the gold core and the number of gold atoms it contains.

In the synthesis process of the yellow-orange-red gold nanoclusters, because the product contains a large number of gold atoms and the core structure is more diverse, the structure of the gold nanoclusters can be controlled by adding ions, adding other metals, changing pH and temperature conditions, and adjusting the properties of ligands, thereby affecting the luminescent properties. Desai et al. synthesized gold nanoclusters emitting orange-red light at 619 nm using 11-MUA containing sulfhydryl groups and turmeric extract (CE) as templates^[38]. It is found that the luminescence intensity of the gold nanoclusters can be adjusted by specific metal ions, and the Cd²⁺ and the Zn²⁺ can be combined with the functional groups on the surface of the gold nanoclusters to adjust the electronic properties of ligands, thereby enhancing the luminescence through chelation and aggregation-induced luminescence emission,Because of its good coordination ability, the Cu²⁺ can coordinate with the ligands, which causes the aggregation of gold nanoclusters and leads to luminescence quenching. The different electronic properties of ligands lead to the change of luminescence of gold nanoclusters with the same number of gold atoms. Sun et al. Found that the emission peak of BSA-stabilized gold nanoclusters doped with silver was blue-shifted, and the emission wavelength was blue-shifted from 630 nm to 570 nm^[39]. With the increase of reaction temperature, the emission peak of Au/Ag nanoclusters in this experiment was red-shifted, and the emission intensity increased first and then decreased. Using Glutathione (GSH) as a template, Jia et al synthesized orange-red luminescent gold nanoclusters with an emission wavelength of 598 nm under ultrasonic conditions, and their luminescence intensity was closely related to temperature^[40]. Wei et al. Changed the reducibility and structure of the template BSA by changing the pH value and synthesis temperature several times during the synthesis, thus changing the interaction between substances and increasing the proportion of monovalent gold in the gold nanoclusters.Red luminescent gold nanoclusters with high quantum yield (23%) were obtained, which is consistent with Luo et al.'S finding that higher proportion of monovalent gold corresponds to stronger luminescence^[41]^[42]. All these show that the synthesis conditions and ligands have an important influence on the luminescent properties.

3.2 Application

Yellow orange-red light has long wavelength, low energy and long transmission distance, which is easy to attract attention in the light, belongs to the sensitive light of human eyes, and is mostly used in the direction of cell imaging. Some red luminescent gold nanoclusters have high photocatalytic performance, which makes them have certain applications in tumor treatment. In the aspect of biosensing, the substance to be detected can control the luminescence signal by causing the aggregation of such gold nanoclusters, thereby causing structural or dimensional changes. This characteristic makes the yellow-orange-red luminescent gold nanoclusters have a good application in biosensing.

By virtue of their ultra-small size and surface charge, gold nanoclusters can enter cells through passive transport and simple diffusion, thus realizing cell imaging. The coupling of gold nanoclusters with various biomolecules can provide good localization ability for specific cells, reduce energy loss in the process of entering cells, and improve efficiency to better achieve cell imaging. The gold nanoclusters synthesized by Pan et al. Using methionine as a template in vitro have strong yellow luminescence (530 nm), and because their ligands can be transported into cancer cells through the plasma membrane by L-type amino acid transporters overexpressed in cancer cells, they can better achieve specific imaging of cancer cells^[43]. Similarly, red luminescent gold nanoclusters were used for cell-specific imaging. Compared with the commonly used nucleic acid dye (CYTO9), the red luminescent gold nanoclusters synthesized with K4 polypeptide had better imaging effect (as shown in Figure 4A). After different times of laser irradiation, the imaging effect of gold nanoclusters was more stable (Figure 4B), the degree of luminescence decay was smaller (Figure 4C), and the photostability was stronger^{[44⇓⇓~47]}. In the process of cell imaging with gold nanoclusters, the principle of targeting is similar, which is to design appropriate materials by combining the biological characteristics of the imaged cells with the specific physical and chemical properties of gold nanoclusters, so as to achieve the purpose of cell visual detection.

The targeting recognition of the partially functionalized red luminescent gold nanoclusters can be focused on tumor cells, while absorbing near-infrared light to generate heat to inhibit the growth of tumor cells, and even kill tumor cells to achieve photothermal therapy. As metal aggregates, gold nanoclusters have a certain photooxidation ability, which can also be used in photodynamic therapy of tumors. Katla et al. Synthesized GSH-stabilized Au₂₅ that can absorb near-infrared light to achieve photothermal therapy of tumors^[48]. Zhu et al. Connected functionalized conjugated polymer (MEH-PPV) on the basis of this gold nanocluster, which improved the photothermal conversion efficiency and realized the integration of tumor imaging and photothermal therapy^[49]. Photodynamic therapy requires special metal oxides or organic compounds as photosensitizers to absorb light and then produce reactive oxygen species to accelerate cell oxidation. However, photosensitizers do not have strong penetration of ultraviolet and visible light into superficial tissues, and the ability to produce reactive oxygen species is not strong enough, which limits the photodynamic therapy of tumors. In recent years, it has been found that gold nanoclusters with good optical properties can be linked to photosensitizers to effectively improve the efficiency of photodynamic therapy. Khlebtsov et al. synthesized a Au₂₀stabilized by BSA and emitting at 660 nm, which has low photooxidation activity. After functionalization with antibody and photosensitizer, the antibody can target tumor cells, and then under 660 nm light irradiation, the integration of imaging and photodynamic therapy can be realized^[50]. The ligands of red luminescent gold nanoclusters have good adsorption ability to drugs, antigens, antibodies and photosensitizers, which will make them have greater application prospects in the field of biomedicine, but Poderys et al pointed out that the cytotoxicity problem in the application of photodynamic therapy needs to be solved^[51].

Desai et al. Found that the principles of Cd²⁺, Zn²⁺ induced luminescence enhancement and Cu²⁺ induced luminescence quenching could be applied to the detection of these ions by gold nanoclusters^[38]. At the same time, it is found that gold nanoclusters also have high sensitivity and effectiveness for the detection and sensing of Hg²⁺^[52,53]. The red luminescent gold nanoclusters (Tf-Au NCs) synthesized by Sha et al. Under microwave-assisted conditions with trivalent gold and transferrin under alkaline conditions can also be used for biosensing detection due to the enhanced luminescence caused by the aggregation of the template^[54]. Serotonin (5-HT), a substance to be detected, can bind to the residues of transferrin, causing aggregation among the gold nanoclusters to cause enhanced luminescence. The detection method of ligand aggregation induced luminescence enhancement has also been proved to be very effective and sensitive, and the same detection principle of aggregation-induced luminescence enhancement has also been applied to the detection of adrenaline^[55]. The red luminescent gold nanocluster synthesized by using the template BSA can be used for biosensing of GSH in living cells, and can also be used as a probe and an inducer for aggregation-induced luminescence enhancement, and is used for sensing and detecting small molecules such as glucose and the like by using a gold nanocluster composite material^[56]^[57].

4 Near-infrared gold nanocluster

4.1 Synthesize

When the excitation wavelength of gold nanoclusters is in the near-infrared region (greater than or equal to 760 nm, invisible to the human eye), the number of gold atoms is more, and most of the biomolecules such as BSA and GSH are used as templates for template synthesis^[58,59]. In order to improve the synthesis efficiency, achieve better size focusing and synthesize gold nanoclusters with precise structure, etching synthesis method is often used. The principles and methods for the synthesis of Au₂₅ with precise atomic numbers have also been clearly reported^[60].

In the near-infrared gold nanoclusters, the ligand has a greater influence on the emission wavelength than the number of atoms. Wan et al. Synthesized near-infrared emitting gold nanoclusters with precise atomic structure by using alkynyl as an uncommon template, and the study of its structure will help us understand the important role of different ligands in the formation of gold nanoclusters^[61]. When the templates are the same, the properties of the templates can be adjusted and controlled by adjusting the molar ratio of synthetic raw materials, adding reducing substances, doping other metals and the like, and the luminescent properties of the gold nanoclusters can also be changed to synthesize the gold nanoclusters with excitation light wavelengths in a near-infrared range. When synthesizing GSH-stabilized near-infrared gold nanoclusters, Qin et al. studied the effect of the molar ratio of raw material GSH to HAuCl₄ on the emission wavelength of the product (as shown in Figure 5). With the decrease of the molar ratio of HAuCl₄ to GSH, the near-infrared emission wavelength of gold nanoclusters tends to decrease, which may be due to the small change in the size of the product caused by the decrease of Au^[62]. When Luo et al. synthesized the Au₂₅ of gold nanoclusters with GSH as the template, they changed the conditions to reduce gold ions with carbon monoxide (CO) on the basis of the synthesis method of red gold nanoclusters. CO not only reduced gold ions in the synthesis process, but also became the ligand of gold nanoclusters in the intermediate products of synthesis.It was found that the complex charge transfer between the ligands and the gold core of the gold nanoclusters prepared by this method resulted in near-infrared emission.Doping other metals (Cu, Zn, Ag, Er) into the gold nanoclusters with near-infrared emission would cause a red shift of the near-infrared emission peak at 1050 nm^[63]^[64].

4.2 Application

Gold nanoclusters with more than 20 gold atoms have near-infrared luminescence, good tissue penetration and thermal effect.Compared with photoproteins and luminophores, better luminescence characteristics will make the image clearer, so the application of near-infrared gold nanoclusters in cell imaging is also very important.

The near-infrared wavelength range is divided into short wavelength (780 ~ 1100 nm) and long wavelength (1100 ~ 2526 nm).Due to the limitation of the synthesis method of gold nanoclusters, the emission wavelength of the synthesized gold nanoclusters is in the short wavelength region. Chen et al synthesized gold nanoclusters with good near-infrared short wavelength emission at 1000 nm using zwitterions and bidentate thiol ligands^[65]. The gold nanocluster has good luminescence quantum yield and good stability under physiological conditions. These properties also allow gold nanoclusters to be used for higher contrast and resolution in vivo imaging in mice (fig. 6). Because of its small size, the gold nanocluster can be quickly cleared by the kidney. Its low toxicity also lays the foundation for the application of near-infrared gold nanoclusters in vivo imaging. The gold nanocluster composite material with near-infrared emission formed by coupling with other molecules can also be well used for biological imaging. Yoo et al. Coupled gold nanoclusters with near-infrared dye molecules with the same good optical properties, and the composite material emitted stronger near-infrared light signals under ultraviolet irradiation, which had better applications in biological imaging^[66].

5 Conclusion and prospect

At present, the synthesis methods of gold nanoclusters with different properties can be essentially classified as template synthesis or etching synthesis. The limited synthesis methods and synthesis templates limit the development of gold nanoclusters, and the problem of size concentration of synthesized products needs to be solved urgently. At the same time, the excellent optical properties of gold nanoclusters have been widely concerned as their outstanding characteristics, but the mechanism of color control is still unclear. In this paper, the synthesis methods and optical properties of gold nanoclusters with various colors are summarized, and the influence of the number of gold atoms on the luminescent color is discussed.The effects of pH, temperature, doping metal, small molecules, ions and other synthesis conditions on the optical properties of gold nanoclusters are proposed, which will provide a certain research basis for discovering the color control mechanism of gold nanoclusters in the future. In this paper, the applications of gold nanoclusters with different luminescence properties are summarized, mainly focusing on biosensing applications relying on template characteristics and luminescence changes, and applications in the field of cell imaging relying on sensitive colors such as green, red and near-infrared emission. In the future, with the discovery of more unknown metabolic pathways in organisms, the biological application of gold nanoclusters will become more extensive and mature.

Gold nanoclusters are promising nanomaterials in international research, and their research fields involve chemistry, physics, biology and other disciplines, which require researchers to integrate knowledge and make innovations. It is possible to control the physical and chemical properties of gold nanoclusters in the future by studying the intrinsic relationship between the synthesis conditions and the structure of gold nanoclusters, and to find potential synthesis methods and new applications. The hot issue of how to apply gold nanoclusters to cancer therapy has also attracted wide attention in recent years, and the application value of gold nanoclusters in cancer therapy has been found.With the in-depth exploration of the optical properties and chemical electronic shell structure changes of gold nanoclusters and the discovery of tumorigenesis, signaling pathways and new drugs, it is expected that gold nanoclusters will be used to achieve new cancer therapy in vivo^[49].

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