The Applications of Gold Nanoparticles in the Diagnosis and Treatment of Gastrointestinal Cancer

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Abstract​

In recent years, the morbidity and mortality of gastrointestinal cancer have remained high in China. Due to the deep location of the gastrointestinal organs, such as gastric cancer, the early symptoms of cancer are not obvious. It is generally discovered at an advanced stage with distant metastasis and lymph node infiltration, making it difficult to cure. Therefore, there is a significant need for novel technologies that can effectively diagnose and treat gastrointestinal cancer, ultimately reducing its mortality. Gold nanoparticles (GNPs), a type of nanocarrier with unique optical properties and remarkable biocompatibility, have the potential to influence the fate of cancer by delivering drugs, nucleic acids to cancer cells and tissues. As a safe and reliable visualization agent, GNPs can track drugs and accurately indicate the location and boundaries of cancer, opening up new possibilities for cancer treatment. In addition, GNPs have been used in photodynamic therapy to deliver photosensitizers, as well as in combination with photothermal therapy. Therefore, GNPs can be used as a safe and effective nanomaterial in the treatment and diagnosis of gastrointestinal cancer.

Keywords: gold nanoparticles, gastrointestinal cancer, ncRNA, imaging, cancer therapy

 

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Introduction​

According to the “2020 Global Cancer Report” recently released by the World Health Organization’s International Agency for Research on Cancer (IARC), the top ten new cancer cases in China in 2020 are as follows: lung, colorectal, gastric, breast, liver, esophageal, thyroid, pancreatic, prostate, and cervical cancers (WHO/IARC published the World Cancer Report 2020). Most of the cases are gastrointestinal cancers, which are closely linked to individuals with high sugar and low fiber diet, helicobacter pylori infection, sedentary, obesity, drinking, and smoking (1–5). They are generally diagnosed at an advanced stage, which seriously impacts the prognosis and life quality of patients. In order to reduce the incidence and mortality of gastrointestinal cancers, as well as improve the survival rate of patients, it is critical to excogitate the treatment and diagnosis of gastrointestinal cancers. In recent years, noble metal nanoparticles have received significant attention in cancer medical research due to their unique efficacy and specificity in imaging, diagnosis, and therapy (6–8). Gold nanoparticles (GNPs) are widely used, particularly in cancer research, because of their ease of synthesis, adjustable size and shape, remarkable biocompatibility, unique optical properties, and surface plasmon resonance (SPR) properties (9–11). Different GNPs have been designed for different types of cancers. The expression of surface receptors, and tumor environment are utilized for photothermal therapy (12), immunotherapy (13), photodynamic therapy (14), gene therapy (15), targeted therapy (16), and a combination of multiple treatments (15), allowing the integration of cancer diagnosis and treatment. This review focuses on the application of GNPs in gastrointestinal cancer.

 

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GNPs With Different Structures​

In 1857, Michael Faraday discovered the light-scattering properties of suspended gold microparticles, which is now known as the Faraday-Tyndall effect (17). Fifty years later, Hirsh et al. found that GNPs irradiated with an electromagnetic wavelength at 820 nm were able to increase the surrounding temperature, which could be used for the treatment of solid tumor (18). In July 2019, the U.S. Food and Drug Administration (FDA) approved an oral drug based on GNPs (CNM-Au8, Clene Nanomedicine, Inc.) for the treatment of amyotrophic lateral sclerosis (ALS) (19). This demonstrated that GNPs are a safe and reliable tool with great potential for disease treatment. The polarization of free electrons and the distribution of surface charges are determined by size (20, 21). GNPs are synthesized in various morphologies, shifting the absorption/scattering peak to the near-infrared window, allowing GNPs in the deep tissue to receive incident light energy (22). Over the last 20 years, many studies have reported GNPs of various shapes, including nanoclusters (23), nanorods (24), nanoplates (25), nanoshells (26), nanocages (27), and nanostars (28), which have widely studied in various cancer. In particular, gold nanorods, nanocages, and nanoclusters have been extensively used in gastrointestinal cancer (Figure 1 ).

 

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Over the last 20 years, many studies have reported GNPs of various shapes, including nanoclusters (23), nanorods (24), nanoplates (25), nanoshells (26), nanocages (27), and nanostars (28), which have widely studied in various cancer. In particular, gold nanorods, nanocages, and nanoclusters have been extensively used in gastrointestinal cancer (Figure 1 ).

 

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Gold Nanorods​

Compared to the other two gold nanoparticles, the gold nanorods have short and long axis directions, with two present wavelengths, which are the plasmon resonance peaks (29). Plasmon resonance can be changed by adjusting the length-to-width ratio or effective volume of the rod (18). Therefore, it can be absorbed by the tumor tissue due to the penetration effect while maintaining a small diameter and better light absorption properties to simultaneously achieve the effect of photothermal treatment (30, 31). Furthermore, studies have shown that gold nanorods modified with low-density lipoprotein binding domain-binding polypeptide (RLT polypeptide) have a relatively evident inhibitory effect in the gastric cancer cell. In addition, they displayed significant anti-tumor efficacy in the treatment of tumors, as well as higher biosafety in vivo compared to the free drug doxorubicin (32). In comparison to the polymer nanomicelles F127 and Clip, a novel gold nanorod that enhances the delivery efficiency of the photodynamic drug aluminum phthalocyanine tetrasulfonic acid (AlPcS4) was developed. This gold nanorod can reduce its ability to bind serum proteins, increase the production of singlet oxygen, induce mitochondrial dysfunction, and reduce mitochondrial membrane potential to activate cell apoptosis, resulting in a highly effective anti-tumor therapy for gastric cancer (33). The EPPT-1 and the myristoylated polyarginine peptide were conjugated to the gold nanorods to target the pancreatic ductal adenocarcinoma (PDA) cells. The novel complex can induced cell death via plasmonic photothermal treatment (PPTT) which shows great promise for developing a new cancer therapy (34). The GNR@Mem was developed to target the oral squamous cell carcinoma (OSCC) and enhance the radiation sensitivity of OSCC cells. Moreover, combined with the photothermal therapy, it shows predominant anti-cancer effect in vivo(35).

 

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Gold Nanocages​

Gold nanocages are a type of gold nanoparticles with a hollow cage-like structure. Compared to the other two gold nanoparticles, they have a high specific surface area, good surface modifiable properties, and a high drug loading rate (36, 37). Hyaluronic acid (HA), anti-GPC-1 antibody, rubescensine A, and gold nanocages were combined to inhibit pancreatic cancer. Furthermore, the multi-mode imaging ability of gold nanocages, including near-infrared fluorescence (NIRF) and magnetic resonance imaging (MRI), can detect pancreatic cancer at an early stage (38). The PDL1 antibody, TGF-β inhibitor, and gold nanocages were combined to form a complex that can selectively target colon cancer cells and accumulate in tumors. In addition to preventing primary tumor growth, the complex also inhibits distant metastasis of colorectal cancer by enhancing the distal effect mediated by synergistic immunotherapy (39). The PPHAuNCsTNCs was constructed with miR-26a loading, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocages. They can accumulate in the HCC, deliver miR-26a to the tumor site and be monitored by fluorescence and photoacoustic tomography imaging (40).

 

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Gold Nanoclusters​

Gold nanoclusters are ultra-small particles composed of several to a few hundred gold atoms (41), that have extremely low cytotoxicity and excellent red fluorescence characteristics that allow them to effectively avoid autofluorescence background in vivo compared to gold nanorods and nanoclusters (42). Moreover, gold nanoclusters coated with folic acid conjugated silica exhibiting excellent red fluorescence optical properties, X-ray absorption, and the ability to target gastric cancer cells, have been successfully developed. They can be used for optical and CT dual-mode imaging of gastric cancer, and have great application potential for early detection of early gastric cancer in vivo(43). The near-infrared fluorescent dye cy5.5 and albumin nanoparticles on the surface of gold nanoclusters can be modified to form an AuNCs/BSA-NPs complex with a significant photothermal effect. Under 808 nm laser irradiation, AuNCs/BSA-NPs can increase the temperature of colorectal cancer tumors on the surface of mice up to 50°C significantly inhibiting tumor growth, while displaying good optical fluorescence imaging properties in HCT116 tumor-bearing mice (44). The AuNCs@GSH-FA were developed with excellent biocompatibility and photostability which could target to gastric cancer to exert great excellent imaging ability for fluorescence/CT dual-mode imaging. This novel complex can acts as a promising diagnostic method for gastric cancer (45).

 

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[syed putra]

Too complicated. The body normally tells you how to defeat diseases and aches but we normally override or ignore these signs.

 

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Too complicated. The body normally tells you how to defeat diseases and aches but we normally override or ignore these signs.

So clever Malaysian Cantonese dog son of prostitute @nightsafari clone now up my thread immediately after you reply to other people’s prostitute thread. Just like how you up slut whore mistress thread around me all the time. 都是来阴的广东狗小人鸡是你妈Pui!

 

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So clever Malaysian Cantonese dog son of prostitute @nightsafari clone now up my thread immediately after you reply to other people’s prostitute thread. Just like how you up slut whore mistress thread around me all the time. 都是来阴的广东狗小人鸡是你妈Pui!

Proof right here @syed putra deliberately up my cancer thread with innocuous comments around other dogs’ prostitute threads