Recent advances in nanoultrasonography for the diagnosis and treatment of gastrointestinal diseases

ABSTRACT

With the rapid development of nanotechnology, nanoultrasonography has emerged as a promising medical imaging technique that demonstrates significant potential in the diagnosis and treatment of gastrointestinal (GI) diseases. This review discusses the applications of nanoultrasonography in the gastrointestinal field, including improvements in imaging resolution, diagnostic accuracy, latest research findings, and prospects for clinical application. By analyzing existing literature, we explore the role of nanoultrasonography in enhancing imaging resolution, enabling targeted drug delivery, and improving therapeutic outcomes, thereby providing a reference for future research directions.

1. Introduction

Gastrointestinal (GI) diseases represent a significant public health concern, with their prevalence steadily increasing globally. Conditions such as obesity, inflammatory bowel disease (IBD), and various functional GI disorders have been linked to a multitude of health complications, including increased morbidity and mortality rates. For instance, obesity has been associated with several GI disorders, highlighting the intricate relationship between metabolic and digestive health [1]. The burden of these diseases not only affects individual patients but also places a strain on healthcare systems, gastrointestinal diseases affect approximately 60 million individuals annually in the United States, leading to healthcare expenditures exceeding $140 billion [2–4], necessitating the need for improved diagnostic and therapeutic strategies.

Traditional ultrasound may not provide sufficient resolution to detect small lesions or subtle changes in the GI tract, making early diagnosis challenging.The accuracy of traditional ultrasound is highly dependent on the operator’s skill and experience, leading to variability in image quality and diagnostic outcomes. Gas-filled intestines can obstruct ultrasound waves, making it difficult to visualize certain areas of the GI tract, particularly in patients with bowel gas or obesity. Conventional ultrasound primarily offers two-dimensional images, which can complicate the assessment of complex anatomical relationships within the GI tract. Traditional ultrasound may struggle to distinguish between different tissue types or lesions, making it hard to differentiate benign from malignant conditions. Traditional ultrasound techniques may not effectively evaluate motility or functional aspects of the GI tract [5].

As such, there is a pressing need for innovative imaging techniques that can overcome these barriers.

Nanotechnology has emerged as a promising field in medical imaging, particularly through the development of nanoscale ultrasound technologies. Nanotechnology can improve the contrast and resolution of ultrasound images, allowing for better visualization of small lesions and subtle abnormalities in the GI tract. Nanoparticles can be engineered to target specific tissues or biomarkers, enhancing the ability to visualize and characterize tumors or inflammatory conditions more accurately. Nanotechnology-enhanced contrast agents can provide superior imaging of blood flow and perfusion, improving the diagnosis of lesions and vascular conditions in the GI tract. Nanotechnology can facilitate real-time imaging and assessment of GI motility and function, providing valuable insights into disorders like gastroparesis or intestinal dysmotility. Advanced imaging techniques using nanotechnology may reduce the variability associated with operator skill, leading to more consistent and reliable results. Nanotechnology can enable the combination of ultrasound with other imaging modalities (e.g., fluorescence imaging), providing comprehensive information about GI conditions. Nanoparticles can be designed to bind to specific biomarkers associated with GI diseases, allowing for earlier detection and more precise characterization of conditions such as cancer or inflammatory bowel disease. Nanotechnology-based ultrasound contrast agents may have improved safety profiles, reducing the risk of adverse reactions compared to traditional agents [6]. The potential applications of nanoultrasound in GI diagnostics could revolutionize the way these diseases are detected and monitored, providing clinicians with critical information that can guide treatment decisions.

This review aims to explore the current state of gastrointestinal diseases, the limitations of traditional ultrasound techniques, and the emerging role of nanoultrasound technology in enhancing diagnostic capabilities. The structure of the article will first outline the epidemiology of GI diseases, followed by a discussion on the limitations of conventional imaging techniques, and finally, an examination of how nanotechnology can address these challenges in clinical practice. Through this exploration, we hope to highlight the importance of integrating advanced technologies into the management of gastrointestinal disorders to improve patient outcomes.

2. Basic principles of nanoultrasonic technology

Nanoultrasonic technology integrates the unique properties of nanoparticles with ultrasound imaging techniques, enabling enhanced diagnostic and therapeutic applications in medicine. At its core, this technology leverages the acoustic characteristics of nanoparticles, which are influenced by their size, shape, and material composition. The interaction of ultrasound waves with these nanoparticles leads to various phenomena, including scattering, absorption, and enhanced contrast in imaging [7]. The acoustic properties of nanoparticles are critical in determining their effectiveness as contrast agents or drug delivery systems. For instance, studies have shown that nanoparticles can significantly alter the propagation of ultrasound waves, enhancing the contrast in imaging applications and enabling the targeted delivery of therapeutics to specific tissues [8,9].

Furthermore, the ability to tailor the acoustic properties of nanoparticles through their synthesis allows for the development of advanced nanomaterials that can respond to specific ultrasound frequencies. This tunability is essential for optimizing their performance in various biomedical applications, such as targeted drug delivery and imaging. For example, the incorporation of metal nanoparticles has been shown to enhance the absorption of ultrasound energy, leading to improved imaging resolution and therapeutic efficacy [10,11].

2.1. Acoustic properties of nanoparticles

An ultrasound transducer generates high-frequency sound waves that penetrate the tissue. These sound waves interact with the tissues and any introduced nanomaterials. When ultrasound waves encounter nanoparticles or microbubbles, they can cause these materials to oscillate or vibrate, enhancing the backscatter of sound waves. This results in improved contrast in the ultrasound images. Nanoparticles can be functionalized with specific ligands that target particular cells or tissues (e.g., cancer cells). When combined with ultrasound, these nanoparticles can be guided to the desired site, where ultrasound can help release therapeutic agents. The use of microbubbles or nanoparticles in the imaging process increases the echogenicity of specific areas, allowing for clearer visualization of structures or lesions. This is particularly useful in identifying tumors or areas of inflammation. Ultrasound can induce mechanical or thermal effects in the targeted area, enhancing the therapeutic efficacy of the delivered agents. For example, ultrasound can increase the permeability of cell membranes (sonoporation), allowing for better drug uptake. Nanoultrasonic imaging allows for real-time monitoring of therapeutic delivery and effectiveness. The imaging can provide immediate feedback on the distribution and accumulation of nanomaterials within the target tissue.

Research indicates that nanoparticles with tailored acoustic properties can significantly improve the efficiency of ultrasound imaging by enhancing the scattering and absorption of ultrasound waves [12,13].

Moreover, the size and shape of nanoparticles play a crucial role in their acoustic performance. For instance, spherical nanoparticles tend to exhibit uniform scattering patterns, while anisotropic nanoparticles can create complex scattering effects, potentially enhancing imaging contrast [14]. The development of composite nanoparticles, such as those combining metals and polymers, has further expanded the potential applications of nanoultrasonic technology, allowing for the design of materials with specific acoustic responses tailored for particular imaging or therapeutic needs [15].

2.2. Working mechanism of nanoultrasonic imaging

Nanoultrasonic imaging operates on the principle of using ultrasound waves to visualize and characterize nanoparticles within biological tissues. When ultrasound waves are transmitted into the tissue, they interact with the nanoparticles, which act as acoustic contrast agents. The resulting echoes are analyzed to generate images that reveal the distribution and concentration of nanoparticles within the tissue [16,17].

The efficacy of nanoultrasonic imaging is enhanced by the specific characteristics of the nanoparticles used, including their size, surface properties, and the ability to respond to ultrasound stimulation. For example, nanoparticles can be engineered to resonate at specific frequencies, leading to enhanced signal generation and improved image contrast [18]. Additionally, the use of microbubbles or nanoparticle-loaded microbubbles can facilitate targeted delivery of drugs and improve the visualization of pathological tissues, such as tumors, by enhancing the ultrasound signal in those areas，illustrated in Figure 1[ [19–22].

Figure 1.

Acoustic properties mechanical characteristics of nanoparticles.

In summary, the working mechanism of nanoultrasonic imaging is a sophisticated interplay between ultrasound technology and engineered nanoparticles, leading to significant advancements in medical imaging and therapeutic interventions. The ongoing research in this field continues to uncover new possibilities for utilizing nanoultrasonic technology in clinical settings, offering promising avenues for improved patient care and treatment outcomes.

3. Applications of nanoultrasound in the diagnosis of gastrointestinal diseases

3.1. Early diagnosis of gastric cancer

Gastric cancer (GC) remains a significant global health concern, characterized by high morbidity and mortality rates. The early detection of gastric cancer is crucial for improving patient outcomes, as the prognosis is significantly better when the disease is caught at an early stage. Gastroscopy is an invasive procedure that can cause discomfort, and there are risks such as bleeding or perforation.Often requires sedation or anesthesia, which can pose risks especially in elderly or high-risk patients. While gastroscopy is effective for visualizing the surface of the stomach, it may have limitations in assessing deeper layers or identifying small lesions.The quality of the procedure and diagnosis can depend significantly on the skill and experience of the operator.nanoultrasound technology has emerged as a promising tool for enhancing the sensitivity and specificity of gastric cancer screening. Nanoultrasound does not require invasive procedures, making it safer and more comfortable for patients.Offers real-time imaging without the need for sedation, allowing for quicker assessments.When used with nanoparticles, nanoultrasound can enhance contrast and provide specific information about tissue characteristics at the molecular level, illustrated in Table 1 [23–25]. Identify high-risk groups for gastric cancer, including individuals with a family history, previous gastric conditions (e.g., atrophic gastritis, gastric ulcers), or populations with a high prevalence of the disease (e.g., certain regions in East Asia). Utilize nanoultrasound for real-time imaging of the stomach. Focus on obtaining clear images of the gastric mucosa, measuring wall thickness, and looking for any abnormalities such as polyps or irregularities. Use ultrasound contrast agents (like microbubbles or targeted nanoparticles) to enhance visualization of suspicious lesions, improving detection of early-stage tumors which might otherwise be missed. Look for early-stage lesions, such as gastric dysplasia or early gastric cancer, which may present as subtle changes in the mucosal layer. An increase in gastric wall thickness (>5 mm) can indicate the presence of malignancy. Evaluate changes in vascularity around lesions, which may suggest malignancy. For instance, studies have demonstrated that integrating nanoultrasound with contrast agents can enhance the imaging of gastric lesions, leading to improved detection rates of early GC [26]. Furthermore, the incorporation of artificial intelligence (AI) into nanoultrasound imaging systems has shown potential in increasing diagnostic accuracy, with some systems achieving diagnostic ratios exceeding 97% for early gastric cancer detection [27]. The ability to visualize lesions at a micro-level not only aids in the identification of early-stage cancers but also provides a noninvasive alternative to traditional endoscopic methods, which can be invasive and uncomfortable for patients.

Table 1.

The advantages and disadvantages of traditional gastroscopy and nanoultrasound in the diagnosis of gastric cancer.

Aspect	Traditional gastroscopy	Nanoultrasound
Advantages	Direct visualization of the gastrointestinal tract	Non-invasive procedure
	Ability to perform biopsies for histological evaluation	Provides real-time imaging without sedation
	Established procedure with extensive clinical use	Higher resolution images at the microstructural level
	Effective for diagnosing lesions and tumors	Potential for early detection at cellular levels
	Can address other gastrointestinal issues (e.g., ulcers)	Lower risk of infection compared to invasive procedures
	Allows for therapeutic interventions (e.g., polypectomy)	Portable and easier to use in various settings
Disadvantages	Invasive and requires sedation in many cases	Still relatively new, with less established guidelines
	Associated risks include bleeding or perforation	Limited availability in some regions
	Discomfort and anxiety for patients	May not provide as comprehensive views as gastroscopy
	Preparation required (e.g., fasting, bowel prep)	Interpretation requires specialized training
	Limited in assessing deeper structures beyond mucosa	Technology still under research for standardization

Nanoultrasound represents a promising advancement in the early screening of gastric cancer, offering a noninvasive, cost-effective means to enhance detection rates. Continued research, technological advances, and supportive clinical data will be necessary to integrate this innovative approach into routine clinical practice effectively. As awareness of its potential grows, nanoultrasound may play a pivotal role in improving early diagnosis and outcomes for patients at risk of gastric cancer.

3.2. Diagnosis of inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, poses diagnostic challenges due to its varied presentations and overlapping symptoms with other gastrointestinal disorders. Traditional ultrasound methods can be limited in their application for IBD, but advancements in technology, such as nanoultrasound, provide new possibilities for imaging and diagnosis. Nanoultrasound technology can capture the intricate details of bowel wall changes and inflammatory processes. Collect detailed patient history to identify symptoms, family history of IBD, and any prior imaging studies. Use a high-frequency ultrasound device capable of nanoultrasound. A smaller, high-frequency transducer will be used to capture detailed images of the bowel wall and surrounding structures. Position the patient comfortably, often in a supine position, to access the abdominal region. Systematically scan the abdominal area, focusing on the small and large intestines. Capture images of the bowel wall thickness, echogenicity, and any abnormalities such as strictures, fistulas, or abscesses. Evaluate surrounding lymph nodes, vascularity, and the presence of free fluid. Increased wall thickness (>3 mm) can indicate inflammation. Alterations in the mucosal pattern and echogenicity can suggest active disease. Look for signs of strictures, fistulas, or abscess formations that are common in Crohn’s disease. Doppler ultrasound can be used to assess increased blood flow to inflamed areas. Analyze the captured images for signs of inflammation, ulceration, and other abnormalities. Correlate ultrasound findings with clinical symptoms and laboratory results for a comprehensive evaluation. Recent studies have indicated that nanoultrasound can effectively differentiate between various forms of IBD and assess disease activity [28]. This imaging modality is particularly beneficial in cases where traditional methods, such as CT or MRI, may fall short in providing clear diagnostic insights. For example, nanoultrasound can detect changes in bowel wall thickness, vascularization, and the presence of complications such as abscesses and strictures with greater sensitivity than conventional imaging techniques [29]. Based on meta-analysis of patient-level data, ultrasound has higher diagnostic accuracy for detecting inflammation in colon than rectum in patients with IBD [30]. By facilitating earlier and more accurate diagnoses, nanoultrasound can guide treatment decisions and improve patient management strategies, illustrated in Table 2 [31–33].

Table 2.

Comparison of nanoultrasound, CT, and MRI in the diagnosis of IBD.

Aspect	Nanoultrasound	CT	MRI
Type of imaging	Non-invasive ultrasound-based imaging	Cross-sectional imaging using X-rays	Cross-sectional imaging using magnetic fields
Contrast agents used	Microbubble and nanoparticle contrast agents	Typically uses iodinated contrast agents	Uses gadolinium-based contrast agents
Radiation exposure	No radiation exposure	Ionizing radiation involved	No radiation exposure
Resolution	High resolution and sensitivity at microstructural level	Good resolution and detail	Excellent soft tissue contrast and detail
Visualization of blood flow	Good visualization of perfusion using contrast agents	Limited vascular information	Good visualization of blood flow
Assessment of inflammation	Direct imaging of inflammatory changes	Good for detecting bowel wall thickening and complications	Excellent for evaluating inflammation and lesions
Detecting complications	Can identify abscesses and fistulas	Excellent for complications (e.g., perforation,obstruction)	Very good for fistula detection and extent of disease
Patient comfort	Generally well-tolerated and no need for sedation	May require contrast administration and involve discomfort	Patients may feel claustrophobic and requires patient cooperation
Cost and accessibility	Generally lower cost, may be more accessible	Relatively high cost and not as readily available in some areas	High cost and requires specialized facilities
Real-time imaging	Provides real-time feedback during imaging	Static images	Static images
Limitations	Operator-dependent, less established than CT/MRI	Risk of radiation, less detail for soft tissue	Longer procedure time, may not be suitable for all patients

3.3. Diagnosis of gastrointestinal tumors

The ability to perform targeted imaging of gastrointestinal tumors using nanoultrasound represents a significant advancement in oncological diagnostics. This technique allows for the visualization of tumors at a cellular level, enhancing the detection of malignancies that may be overlooked by standard imaging methods. Nanoultrasound utilizes targeted contrast agents that bind specifically to tumor markers, thus providing a clearer delineation of tumor boundaries and characteristics [34]. This targeted approach not only improves the accuracy of tumor detection but also aids in the assessment of tumor response to therapies, enabling personalized treatment plans. Targeted imaging of gastrointestinal tumors using nanoultrasound is an innovative approach that leverages advancements in ultrasound technology to enhance the detection and characterization of tumors in the gastrointestinal (GI) tract. Collect comprehensive patient history, including symptoms, prior imaging studies, and any family history of cancer. The patient may need to fast before the scan to reduce bowel gas and improve visualization. Select an ultrasound machine capable of high-frequency imaging with specialized probes designed for nanoultrasound. Utilize high-frequency transducers to achieve better resolution when imaging the GI tract. The patient should be positioned comfortably, typically in a supine or lateral position for optimal access to the abdominal area. Start scanning the abdomen with a focus on areas of concern identified from clinical evaluation. Create transverse and longitudinal images of the GI tract, looking closely for abnormalities. Pay special attention to the lesions suspected to be tumors, evaluating their size, shape, echogenicity, and borders. Using targeted nanoparticles as contrast agents can enhance the ultrasound signal from tumor areas. These particles selectively accumulate in tumor tissue, providing a clearer image. Nanoparticles can be engineered to bind to tumor-specific biomarkers, improving the specificity of tumor detection. Evaluate size, shape, echogenicity (hypo- or hyperechoic), and vascularity. Check for signs of local invasion into surrounding structures, as well as lymph node involvement. Assess lesions in relation to surrounding normal tissue. Trained specialists analyze the images for features indicative of malignancy (e.g., irregular borders, increased blood flow). Integrate imaging results with clinical symptoms and other diagnostic findings to refine diagnosis. Nanoultrasound represents a promising advancement in the imaging of gastrointestinal tumors, offering the potential for improved detection and characterization of malignant lesions. As technology evolves, ongoing research and clinical trial evaluations will be essential to establish protocols and validate the effectiveness of nanoultrasound in routine clinical practice for gastrointestinal. Recent research has highlighted the effectiveness of nanoultrasound in identifying gastrointestinal tumors, including those associated with elevated carcinoembryonic antigen (CEA) levels, which are common in various gastrointestinal cancers [35]. The use of gold nanoparticles as contrast agents resulted in a 30% increase in diagnostic accuracy compared to standard ultrasound techniques. The researchers concluded that the integration of nanotechnology not only improved the detection of gastric tumors but also provided valuable information regarding tumor vascularity, which is crucial for treatment decisions [36]. The integration of nanoultrasound with other imaging modalities, such as PET and MRI, could further enhance the diagnostic capabilities and therapeutic monitoring of gastrointestinal tumors, paving the way for more effective interventions and improved patient outcomes, illustrated in Table 3 [37–40].

Table 3.

Common contrast agents and their characteristics and applications for nanoultrasound diagnosis of cancer.

Contrast Agent	Type	Type	Clinical applications
Sonovue (Sulfur hexafluoride)	Microbubble	Enhances echogenicity, improving visualization of blood flow and lesions	Imaging for liver and gastric tumors
Lumason (Sonazoid)	Microbubble	Provides dual-mode imaging; can assess both vascularity and tissue perfusion	Gastric cancer imaging and liver lesions
Definity (Perflutren lipid microspheres)	Microbubble	Gas-filled microbubbles enhance ultrasound signals for better imaging	Helps visualize abdominal and gastric structures
Gold nanoparticles	Nanoparticle	Provides high contrast on ultrasound when functionalized for targeting cancer cells	Experimental use in targeted gastric cancer imaging
Liposome-based nanoparticles	Nanoparticle	Can encapsulate imaging agents and deliver them to specific tumor sites	Potential applications in gastric cancer diagnostics and therapy
Microbubble contrast agents with targeted molecules	Targeted microbubble	Functionally designed to bind specific tumor markers on gastric cancer cells	Targeting and imaging of gastric tumors

4. Applications of nanoultrasound in gastrointestinal disease treatment

4.1. Local drug delivery guided by nanoultrasound

Local administration of therapies for gastrointestinal diseases guided by nanoultrasound is an emerging approach that aims to enhance precision medicine in the management of various GI conditions. Nanoultrasound technology has emerged as a promising approach for local drug delivery in the treatment of gastrointestinal diseases. This technique utilizes ultrasound waves to enhance the penetration and distribution of therapeutic agents at targeted sites, thereby improving treatment efficacy while minimizing systemic side effects. The integration of ultrasound-responsive nanocarriers allows for controlled drug release triggered by ultrasound, which can significantly increase the concentration of drugs in the desired area. Conduct a comprehensive evaluation of the patient, including history and physical examination, to identify the specific GI condition and the targeted area for treatment. Patients may need to undergo fasting to minimize bowel gas and optimize imaging conditions. Use a high-frequency ultrasound machine with appropriate transducers to visualize the targeted area within the gastrointestinal tract. Perform real-time ultrasound imaging to identify lesions, assess their characteristics, and determine the optimal approach for local therapy. Nanoultrasound can guide injections of therapeutics (e.g., steroids, chemotherapeutics, biologics) directly into lesions or affected areas, ensuring targeted delivery. Utilize nanoparticles or microspheres that can encapsulate drugs and be targeted to specific lesions, enhancing localization and effectiveness. Use ultrasound to guide thermal ablation techniques (e.g., radiofrequency ablation, microwave ablation) for tumors, enabling precise treatment while minimizing damage to surrounding healthy tissue, as illustrated in Figure 2. Formulate drugs in nanoparticles that can be activated or enhanced by ultrasound, improving their uptake within target tissues. Nanoparticles can be engineered to target specific receptors on tumor cells, which allows for more effective local treatment. Use nanoultrasound to assess the immediate response to the treatment and ensure proper delivery of the therapeutic agent. Schedule follow-up imaging to monitor the therapeutic effects, identify any complications, and determine the need for additional interventions. Benefits of Nanoultrasound-Guided Local Administration: Targeted treatment reduces systemic exposure and potential side effects. The ability to visualize structures in real-time during administration enhances accuracy and safety. Enhanced delivery via nanoparticles can improve the therapeutic index of drugs. Safety Considerations: Ensure that patients are adequately informed about the procedure’s risks and benefits. Follow strict aseptic techniques during local administration to prevent infection. Monitor patients for immediate reactions post-procedure. Studies have shown that ultrasound-mediated nano-drug delivery systems can effectively overcome biological barriers, such as tissue heterogeneity and vascular permeability, facilitating targeted therapy for conditions like gastric and colorectal cancers [41,42]. Additionally, the use of stimuli-responsive nanocarriers, which release drugs in response to ultrasound, has demonstrated improved therapeutic outcomes in preclinical models of gastrointestinal malignancies [43,44]. This localized approach not only enhances drug bioavailability but also reduces the risk of adverse effects associated with systemic drug administration, making it a valuable strategy in the management of gastrointestinal diseases.

Figure 2.

Local drug delivery guided by nanoultrasound.

Local administration of therapies guided by nanoultrasound represents a promising approach in managing various gastrointestinal diseases, allowing for targeted, minimally invasive treatments. As research continues, more tailored protocols will likely evolve, enhancing the effectiveness and safety of therapeutic interventions in gastroenterology.

4.2. Ultrasound-mediated tumor ablation techniques

Ultrasound-mediated tumor ablation is an advanced therapeutic technique that utilizes focused ultrasound energy to destroy tumor cells non-invasively. This method has gained attention for its ability to target tumors precisely while sparing surrounding healthy tissue. Ultrasound-mediated tumor ablation techniques have gained traction as minimally invasive options for treating gastrointestinal tumors, particularly in the liver and pancreas. High-Intensity focused ultrasound (HIFU) and ultrasound targeted microbubble destruction (UTMD) are among the leading modalities that leverage ultrasound’s ability to induce localized thermal effects or mechanical disruptions to destroy cancerous tissues. HIFU is the most commonly used technique for tumor ablation. HIFU utilizes focused ultrasound waves to generate heat, effectively ablating tumors while sparing surrounding healthy tissues [45,46]. The ultrasonic energy heats the tumor tissue to temperatures typically between 60°C and 100°C, leading to coagulative necrosis and apoptosis (programmed cell death). Conduct a comprehensive evaluation of the patient to determine the suitability of ultrasound-guided ablation for specific tumor types, sizes, and locations. Ultrasound imaging is used to locate the tumor and to guide the delivery of ultrasound energy accurately. The ultrasound transducer is placed over the tumor area, and focused ultrasound energy is delivered intermittently to achieve desired temperatures and treatment effect. Real-time imaging allows for monitoring tumor response during the procedure and ensures effective treatment. Furthermore, UTMD enhances drug delivery and cellular uptake by increasing the permeability of cell membranes through sonoporation, making it a dual-function technique that not only ablates tumors but also facilitates targeted drug delivery [47,48]. Recent studies have demonstrated the efficacy of these techniques in achieving significant tumor reduction and improved patient outcomes, highlighting their potential as standard treatments in gastrointestinal oncology [49,50]. This technique often requires no incisions, leading to reduced recovery times, lower complication rates, and minimal postoperative pain. Ultrasound provides real-time imaging, allowing for immediate assessment of treatment efficacy. The focused nature of the treatment minimizes collateral damage to surrounding healthy tissues.

Ultrasound-mediated tumor ablation represents a promising and innovative approach to cancer treatment, providing a noninvasive option for targeted tumor destruction. As the technology advances and clinical research continues, we can anticipate broader applications and refined techniques that could significantly impact cancer management.

4.3. Prospects of nanoultrasound in targeted therapy

The future of nanoultrasound in targeted therapy for gastrointestinal diseases looks promising, with ongoing research focusing on enhancing the specificity and efficacy of treatment modalities. Nanoultrasound provides high-resolution imaging, allowing for detailed visualization of GI tumors and lesions. This capability aids in accurately locating target sites for therapy. The ability to visualize changes in real-time facilitates dynamic monitoring of disease progression and treatment response. The development of smart nanocarriers that can respond to ultrasound stimuli for controlled drug release is at the forefront of this field. These nanocarriers are designed to selectively release their payloads in response to ultrasound exposure, allowing for precise treatment of tumors while minimizing damage to surrounding healthy tissues [41,51]. Additionally, the combination of nano ultrasound with other therapeutic modalities, such as immunotherapy and gene therapy, is being explored to further enhance treatment outcomes [52,53]. In conditions like IBD, nanoultrasound can be used to deliver anti-inflammatory drugs directly to the affected area, improving therapeutic outcomes and reducing side effects. Utilizing ultrasound to control the release of encapsulated drugs offers a method of on-demand therapy, providing treatment precisely when and where it is needed. The use of nanoultrasound-guided therapies may provide alternatives to surgical interventions for certain GI conditions, leading to lower morbidity and faster recovery times for patients. Techniques that minimize invasiveness are generally more acceptable to patients, potentially leading to better compliance and outcomes. Nanoultrasound can support personalized treatment strategies by using imaging data to assess individual lesion characteristics and guide therapy selection. Real-time imaging allows for adjustments in treatment plans based on the immediate response of the tumor to therapy. Ongoing research into novel nanoparticles, ultrasound parameters, and therapeutic compounds will drive advancements in how nanoultrasound can be applied to GI diseases. As the technology matures, well-designed clinical trials will be essential to evaluate the safety and efficacy of nanoultrasound-guided therapies in different types of GI diseases. The integration of real-time imaging techniques with nanoultrasound also holds potential for improving treatment accuracy and monitoring therapeutic responses. As research progresses, the application of nanoultrasound in targeted therapy is expected to revolutionize the management of gastrointestinal diseases, offering more effective and personalized treatment options for patients.

The application prospects of nanoultrasound in targeted therapy for gastrointestinal tract diseases are promising, offering significant potential for enhancing the diagnosis, treatment, and monitoring of various conditions. Continued advancements in technology and further research will be crucial in realizing the full potential of nanoultrasound and improving patient outcomes in gastrointestinal medicine.

5. Latest research achievements

5.1. Recent clinical trial reviews

Recent clinical trials have significantly advanced our understanding of various medical conditions and treatments. For instance, studies focusing on stem cell therapy for traumatic brain injury (TBI) have shown promising results. A systematic review of clinical trials from 2013 to 2023 revealed that stem cell transplantation leads to neurological improvements in TBI patients, with no serious adverse events reported, indicating the safety and feasibility of this approach [54]. Similarly, ongoing trials in pancreatic cancer have introduced novel therapies, including immunotherapy and targeted therapies, aiming to improve survival rates in this aggressive disease [55]. Moreover, the landscape of tuberculosis treatment has evolved with new drugs and clinical trials demonstrating efficacy in both drug-susceptible and drug-resistant cases [56]. These trials underline the importance of continuous research and the need for large-scale studies to validate findings and optimize treatment protocols.

5.2. Comparison analysis of nanoultrasound and other imaging technologies

The emergence of nanoultrasound as a diagnostic tool presents a compelling alternative to traditional imaging techniques such as MRI and CT. nanoultrasound utilizes nanomaterials to enhance imaging resolution and contrast, making it particularly useful in identifying small lesions and vascular structures. Recent studies have demonstrated that nano-contrast agents significantly improve ultrasound imaging quality, allowing for better visualization of tumors compared to conventional methods [57]. In contrast, while MRI and CT offer detailed anatomical information, they often involve exposure to ionizing radiation and higher costs. Furthermore, the advancements in ultrasound technologies, such as contrast-enhanced ultrasound (CEUS) and elastography, have shown to be effective in various clinical applications, including cardiology and oncology, highlighting the versatility of ultrasound in modern diagnostics [58]. The integration of nano-technology into ultrasound imaging holds the potential to revolutionize diagnostic practices, offering a safer, cost-effective, and highly accurate alternative.

5.3. Development of novel nanomaterials and their application prospects

The development of novel nanomaterials has opened new frontiers in various biomedical applications, particularly in drug delivery, imaging, and therapeutics. Recent advancements have highlighted the potential of nanomaterials such as gold nanoparticles, liposomes, and polymeric nanoparticles in enhancing drug solubility, bioavailability, and targeted delivery [59]. For example, the use of PEG-PLLA nanoparticles has shown promise in dual-mode imaging for tumor diagnosis, combining ultrasound and magnetic resonance imaging techniques [57]. Furthermore, nanomaterials are being investigated for their role in combating multidrug-resistant bacterial infections, with research demonstrating their effectiveness in delivering antibiotics directly to infected sites, thus minimizing systemic toxicity [59]. The application of nanotechnology in regenerative medicine, particularly in tissue engineering, has also gained traction, with studies exploring the use of nanomaterials to enhance cell proliferation and differentiation [60]. As research continues to evolve, the prospects for nanomaterials in clinical settings appear promising, paving the way for innovative therapies and diagnostic tools that could significantly improve patient outcomes.

6. Conclusion

In conclusion, the application of nanoultrasound technology in the field of gastrointestinal diseases demonstrates significant potential that could transform diagnostic and therapeutic practices. This innovative approach leverages the unique properties of nanomaterials to enhance ultrasound imaging, providing a higher resolution and more accurate depiction of gastrointestinal structures and pathological changes. As highlighted throughout this review, the precision offered by nanoultrasound can lead to earlier detection of conditions such as inflammatory bowel disease and gastrointestinal cancers, ultimately improving patient outcomes.

However, while the advantages of nanoultrasound are clear, it is crucial to balance the findings from various studies that report differing results regarding its efficacy and safety. Some research indicates promising diagnostic capabilities, while others raise concerns about biocompatibility and long-term effects of nanoparticles in the human body. As experts in the field, we must synthesize these varying perspectives and focus on collaborative efforts to establish standardized protocols and guidelines for the clinical application of nanoultrasound.

Looking ahead, future research should prioritize addressing key issues such as the optimization of nanoparticle design for specific gastrointestinal applications, the development of rigorous safety assessments, and the establishment of clear metrics for evaluating the technology’s diagnostic performance. Additionally, interdisciplinary approaches that integrate insights from nanotechnology, imaging science, and clinical medicine will be vital in overcoming current limitations and maximizing the benefits of nanoultrasound.

In summary, while nanoultrasound offers a promising frontier in the management of gastrointestinal diseases, a holistic and balanced approach to research and application will be essential for realizing its full potential. The ongoing dialogue among researchers, clinicians, and technologists will not only advance our understanding but also ensure that this innovative technology is deployed safely and effectively within clinical settings.

7. Future perspective

7.1. Feasibility of nanoultrasound in clinical practice

The integration of nanoultrasound technology into clinical practice presents a promising avenue for enhancing diagnostic capabilities and therapeutic interventions. The feasibility of this technology is underscored by its ability to provide high-resolution imaging at a cellular level, which is particularly beneficial in the early detection of diseases such as cancer. Recent studies have demonstrated that nanoultrasound can improve the visualization of tumor margins, aiding in more precise surgical planning and execution, thus potentially reducing recurrence rates and improving patient outcomes [61]. Furthermore, the use of nanoparticles in ultrasound imaging enhances contrast and specificity, allowing for the targeted delivery of therapeutic agents alongside imaging, thereby facilitating personalized medicine approaches [62]. The transformative potential of nanoultrasound technology in medical imaging, particularly for gastrointestinal diseases, is increasingly recognized. As we expand the discussion to include regulatory challenges, biocompatibility, toxicity, long-term safety, and patient acceptance factors, we aim to provide a comprehensive understanding of the landscape surrounding the clinical adoption of this innovative technology. The integration of nanoparticles in medical applications faces several regulatory hurdles. Regulatory bodies such as the FDA and EMA require extensive preclinical and clinical data to ensure the safety and efficacy of nanomaterials. This process can be time-consuming and costly, often deterring innovation. Nanoparticles may be classified differently depending on their properties and intended use, complicating the approval pathway. Clear guidelines and frameworks are needed to streamline this process. A lack of standardized protocols for the characterization and testing of nanoparticles can lead to variability in results and hinder the ability to compare studies. Continuous monitoring of nanoparticle safety after market approval is essential. Establishing robust post-market surveillance systems can help track long-term effects and ensure ongoing patient safety. Recent findings highlight the importance of biocompatibility and toxicity assessments for nanoparticles used in medical applications [63]. Research has demonstrated that surface modifications on nanoparticles can significantly enhance their biocompatibility, reducing immune responses and cytotoxic effects [64]. Comprehensive toxicity assessments are crucial. Recent studies have reported that certain nanoparticles may accumulate in organs over time, raising concerns about long-term exposure [65]. Evaluating the biodistribution and potential chronic effects of nanoparticles is vital for ensuring their safety in clinical settings. Longitudinal studies are necessary to assess the long-term safety of nanoparticles. Research focusing on the chronic effects of exposure and potential accumulation in tissues can provide valuable insights into their long-term safety profiles. Understanding patient acceptance is critical for the successful adoption of nanoultrasound technology. Key factors influencing patient acceptance include: Nanoultrasound should maintain the noninvasive nature of traditional ultrasound, which is generally well-accepted by patients. Ensuring that the procedure is comfortable and quick can enhance patient willingness to undergo nanoultrasound imaging. Providing clear information about the procedure, its benefits, and safety can alleviate patient concerns and improve acceptance. The cost of nanoultrasound technology must be competitive with existing imaging modalities. While initial implementation costs may be high, the potential for improved diagnostic accuracy and reduced need for invasive procedures could lead to cost savings in patient management. Ensuring that insurance plans cover nanoultrasound procedures will be crucial for patient accessibility and acceptance. Nanoultrasound offers enhanced sensitivity and specificity, potentially leading to earlier diagnosis and better treatment outcomes compared to conventional ultrasound, CT scans, or MRI. Highlighting these advantages can encourage both patients and healthcare providers to consider nanoultrasound as a viable option. Concerns about the safety and efficacy of new technologies can serve as barriers to acceptance. Addressing these concerns through education and transparent communication about the technology’s benefits and risks is essential [66]. Addressing these challenges will be crucial for the successful implementation of nanoultrasound technology in clinical practice.

7.2. Technology promotion and patient acceptance

The promotion of nanoultrasound technology within clinical settings hinges significantly on patient acceptance. Factors influencing acceptance include the perceived benefits of the technology, such as improved diagnostic accuracy and reduced invasiveness compared to traditional imaging methods [67]. Educational initiatives aimed at both healthcare providers and patients are essential to enhance understanding and trust in nanoultrasound technology. Research indicates that patients are more likely to accept new technologies when they are informed about the safety, efficacy, and potential benefits of the procedures [68]. Additionally, the integration of digital health solutions, such as telemedicine and mobile health applications, can facilitate greater patient engagement and acceptance of new diagnostic modalities like nanoultrasound [69]. However, barriers such as concerns over data privacy, the complexity of technology, and varying levels of health literacy among patients must be addressed to foster a supportive environment for the adoption of nanoultrasound in clinical practice.

7.3. Future research directions and development trends

Future research directions in the realm of nanoultrasound technology should focus on enhancing imaging capabilities and therapeutic applications through innovative engineering and material science advancements. The development of multifunctional nanoparticles that can simultaneously provide imaging and therapeutic benefits is a promising area of exploration [70]. Furthermore, research should also investigate the long-term safety and efficacy of nanoultrasound applications in diverse clinical scenarios, including chronic diseases and personalized medicine [71]. Collaborative efforts between academia, industry, and clinical practitioners will be vital in translating laboratory findings into practical applications. Despite the promising results, several limitations in current studies should be acknowledged: Many studies have small sample sizes or lack diversity in patient populations, which can limit the generalizability of findings. There is a need for standardized protocols for the use of nanomaterials in ultrasound imaging to ensure consistency in results and facilitate comparison across studies. Most current research focuses on short-term outcomes. Longitudinal studies are needed to assess the long-term efficacy and safety of nanoultrasound applications in clinical practice. The clinical translation of nanotechnology in ultrasound imaging faces regulatory challenges, which may delay the widespread adoption of these techniques. Additionally, the exploration of artificial intelligence and machine learning algorithms for data analysis in nanoultrasound imaging could significantly enhance diagnostic accuracy and operational efficiency [72]. Overall, a concerted focus on overcoming existing challenges, coupled with innovative research and technology integration, will pave the way for the successful adoption of nanoultrasound in clinical settings.

Funding Statement

This paper was not funded.

Article highlights

Applications of nanoultrasound in the diagnosis of gastrointestinal diseases

• Nanoultrasound can provide higher resolution images, potentially allowing for the detection of smaller lesions not visible with traditional methods.

• Nanoultrasound technology is revolutionizing the imaging landscape for IBD by providing high-resolution images that can capture the intricate details of bowel wall changes and inflammatory processes.

• Nanoultrasound can effectively differentiate between various forms of IBD and assess disease activity.

• Nanoultrasound can detect changes in bowel wall thickness, vascularization, and the presence of complications such as abscesses and strictures with greater sensitivity than conventional imaging techniques.

• Nanoultrasound utilizes targeted contrast agents that bind specifically to tumor markers, thus providing a clearer delineation of tumor boundaries and characteristics

Applications of nanoultrasound in gastrointestinal disease treatment

• Nanoultrasound technology has emerged as a promising approach for local drug delivery in the treatment of gastrointestinal diseases. This technique utilizes ultrasound waves to enhance the penetration and distribution of therapeutic agents at targeted sites, thereby improving treatment efficacy while minimizing systemic side effects.

• Ultrasound-mediated tumor ablation is an advanced therapeutic technique that utilizes focused ultrasound energy to destroy tumor cells non-invasively.

• HIFU utilizes focused ultrasound waves to generate heat, effectively ablating tumors while sparing surrounding healthy tissues.

• The future of nanoultrasound in targeted therapy for gastrointestinal diseases looks promising, with ongoing research focusing on enhancing the specificity and efficacy of treatment modalities. Nanoultrasound provides high-resolution imaging, allowing for detailed visualization of GI tumors and lesions.

Latest research achievements

• Ongoing trials in pancreatic cancer have introduced novel therapies, including immunotherapy and targeted therapies, aiming to improve survival rates in this aggressive disease.

• The emergence of nanoultrasound as a diagnostic tool presents a compelling alternative to traditional imaging techniques such as MRI and CT.

• The integration of nano-technology into ultrasound imaging holds the potential to revolutionize diagnostic practices, offering a safer, cost-effective, and highly accurate alternative.

• The development of novel nanomaterials has opened new frontiers in various biomedical applications, particularly in drug delivery, imaging, and therapeutics.

Author contributions

Weiping Wan: data gathering and organization; writing initial manuscript; Haina Tao: writing and reviewing initial manuscript; Zhixiao Chen: writing and reviewing initial manuscript; Fangming Guo&Yun Tian: conception and design of the study; review and finalization of the manuscript; supervision and guidance of the work and finalization of the manuscript. All the authors read the final manuscript and agreed to publish this work.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.