Optical imaging technologies rely on the interaction between light and biological tissues to capture imaging information. As photons traverse tissue, they undergo processes such as absorption, scattering, and emission, which carry detailed structural and functional data of the tissue. Label-free optical microscopy, due to its non-invasive, non-destructive, and fast detection characteristics, is widely used for imaging and sensing at the microscopic scale. For example, advanced optical microscopy systems have demonstrated the ability to capture high signal-to-noise and high-contrast images of single protein molecules, gold nanoparticles, and perovskite nanocrystals in real-time.
In contrast, computed tomography (CT) imaging is based on the differential attenuation of X-rays as they pass through various tissues. Denser tissues (e.g., bones) cause greater attenuation of X-rays, while less dense tissues (e.g., lungs) attenuate X-rays to a lesser extent. These attenuation differences are captured by detectors and reconstructed by computer algorithms to form cross-sectional images. CT offers high spatial resolution, deep tissue penetration, low cost, and short scan times, making it one of the most common imaging techniques.
The contrast mechanisms of nanoparticles in optical and CT imaging are fundamentally different. In optical imaging, nanoparticles primarily generate contrast by scattering and absorbing light. For instance, metal nanoparticles such as gold exhibit strong light scattering due to surface plasmon resonance when illuminated, significantly enhancing the scattered light signal. Researchers have developed scattering light imaging technologies that leverage nanoparticles' scattering properties for real-time observation of non-labeled nanoparticles under confocal microscopy.
In CT imaging, nanoparticles provide contrast by enhancing the attenuation of X-rays. Elements with high atomic numbers (e.g., gold, bismuth, iodine) exhibit higher X-ray attenuation, making them ideal CT contrast agents. Gold nanoparticles are particularly attractive due to their excellent biocompatibility, stable physicochemical properties, and ease of chemical synthesis and functionalization, positioning them as ideal CT tracers for imaging applications. Additionally, ultra-small Bi2S3 nanoparticles, with their large X-ray attenuation coefficient, have also been widely investigated as CT contrast agents.
Multimodal imaging integrates the advantages of different imaging techniques to overcome the limitations of single-modality imaging. For instance, the combination of CT and MRI creates a complementary approach, where CT compensates for MRI's limitations in imaging bone and calcified tissues, while MRI offers superior soft tissue contrast. In PET/CT combinations, PET provides metabolic information, while CT delivers high-resolution anatomical details. The combined use of these modalities can offer comprehensive insights into disease mechanisms and accurate lesion localization.
By simultaneously enhancing imaging in two or more modalities with a single injection, multimodal imaging maximizes the strengths of each imaging technique, resulting in more accurate and comprehensive diagnostic information. For example, combining CT with fluorescence imaging brings together CT's high spatial resolution and fluorescence imaging's high sensitivity, enabling simultaneous structural and functional imaging.
Fig.1 Nanomaterial-based CT agents for enhanced imaging and therapy1,2.
Quantum dots are semiconductor nanocrystals that exhibit size-dependent fluorescence properties. By controlling their size and composition, the emission wavelength can be tuned, covering the ultraviolet to near-infrared spectrum. Compared to traditional organic dyes, quantum dots offer superior fluorescence brightness, better photostability, and longer fluorescence lifetimes, making them ideal for long-term biological imaging applications. In multifunctional nanoparticle contrast agent design, quantum dots are often combined with other materials to form composite probes. For example, MPt (M = Fe, Co, or Ni) alloy nanoparticles, which exhibit good biocompatibility and high X-ray attenuation, provide an excellent platform for constructing CT/T1-MRI dual-modality contrast agents. These multifunctional nanoparticles can not only enhance CT contrast but also improve MRI signals due to their magnetic properties, facilitating dual-modality imaging.
Gold and silver nanoclusters consist of a few to several hundred metal atoms, with sizes typically smaller than 2 nanometers. These clusters exhibit unique molecular-like properties, including discrete electronic energy levels and size-dependent fluorescence emission. Gold nanoparticles, with their high X-ray attenuation capabilities, are excellent CT contrast agents. Moreover, gold nanoparticles have been widely applied in imaging stem cells in vivo due to their biocompatibility and stability. Silver nanoparticles also find unique applications in optical imaging. Scattering light imaging technologies have been developed to visualize silver nanoparticles within cells. These nanoparticles scatter light in a similar manner to dust particles scattering sunlight, allowing for real-time observation under confocal microscopy.
Upconversion nanoparticles are materials that can absorb low-energy light (such as near-infrared) and emit higher-energy light (such as visible light). This anti-Stokes fluorescence property provides significant advantages for biological imaging, as near-infrared light experiences less scattering and absorption in tissues, allowing for deeper tissue penetration while minimizing background autofluorescence and enhancing the signal-to-noise ratio. Upconversion nanoparticles typically consist of a host matrix doped with rare-earth ions, and their upconversion efficiency can be improved by carefully designing core-shell structures. These nanoparticles can be integrated with other imaging modalities to construct multifunctional imaging platforms. For example, combining upconversion nanoparticles with gold nanostructures allows for dual-modal imaging that takes advantage of both upconversion luminescence and gold nanoparticle-enhanced CT contrast.
Near-infrared (NIR) probes are imaging agents that absorb and emit light within the near-infrared region (700–1700 nm). Because biological tissues exhibit minimal absorption and scattering in this range, NIR light can penetrate deeper into tissues, making it ideal for in vivo imaging. NIR probes include organic dyes, quantum dots, gold nanoclusters, and single-walled carbon nanotubes, among others. In CT/fluorescence dual-modality imaging studies, oil-soluble ICG-Der-01 fluorescent dye has been combined with iodized oil to create a dual-modality nanoparticle contrast agent. These iodized oil nanoparticles exhibit strong fluorescence emission in the NIR region, while the iodine content provides CT contrast, enabling the simultaneous tracking of their distribution in biological systems using both imaging modalities.
Combining NIR probes with upconversion nanoparticles can further enhance the depth and resolution of optical imaging. For example, adjusting the emission wavelength of upconversion nanoparticles to the second near-infrared window (1000–1700 nm) can significantly improve imaging depth and spatial resolution, providing new solutions for deep tissue optical imaging. Nanoparticles in optical and CT imaging are rapidly evolving, transitioning from single-modality imaging to multimodal approaches, and expanding their applications from ex vivo to in vivo imaging. With the ongoing development of novel nanoparticles and imaging technologies, the application of nanoparticles in multimodal imaging will become more extensive and refined, providing valuable tools for advanced biomedical research.
BOC Sciences offers cutting-edge nanoparticles tailored for diagnostic imaging applications. Our customizable solutions are designed to enhance precision and sensitivity in detection.
Gold-based nanoparticles (AuNPs) have emerged as promising contrast agents for CT imaging due to their high atomic number (Z=79) and strong X-ray attenuation properties. The ability of gold nanoparticles to absorb X-rays makes them ideal candidates for enhancing CT imaging contrast. Among gold nanoparticles, gold nanorods, a specific form of gold material, have gained attention due to their unique shape and size, offering improved potential for CT imaging contrast enhancement. These gold nanorods exhibit superior X-ray attenuation properties, further enhancing CT image quality, resolution, and contrast. To further optimize the CT imaging performance of gold nanoparticles, researchers have focused on structural design and surface functionalization strategies. For example, by combining gold nanoparticles with dendritic macromolecules to form nanocomposites, studies have shown that these composite materials exhibit promising potential in biological CT imaging. These materials not only provide excellent X-ray attenuation but also demonstrate good biocompatibility and surface functionalization, paving the way for targeted CT imaging applications.
Bismuth-based nanomaterials are another class of promising CT contrast agents due to their high atomic number (Z=83) and strong X-ray attenuation ability. Bismuth elements provide an effective means of enhancing the X-ray contrast, making them suitable for tumor imaging and other diagnostic applications. Additionally, bismuth nanomaterials show significant potential in combined imaging modalities such as photoacoustic (PA) imaging and therapeutic applications, which extend their use beyond CT imaging.
Tungsten oxide nanoparticles (WO3₋x@BSA) have also emerged as valuable CT contrast agents. Research has demonstrated that tungsten-based materials outperform traditional iodine-based contrast agents in terms of CT value, especially at comparable concentrations. Tungsten oxide nanoparticles provide higher image density and contrast in CT scans, making them an attractive candidate for future CT imaging applications. Animal studies further confirm that tungsten oxide nanoparticles, when injected through various routes into rodents, accumulate in different organs and tissues, resulting in high-density CT signals and supporting their viability as CT contrast agents.
Rare-earth doped nanocomposites, particularly those based on rare-earth fluorides, have unique advantages in CT imaging. For example, NaLuF4:20%Gd3+ nanoparticles have been explored for CT imaging, and studies have shown that the CT values of these nanoparticles correlate linearly with concentration within a range of 0.2–10.0 g/L, making them valuable for in vivo distribution assessment. The linear relationship between the CT value and nanoparticle concentration allows for more accurate quantitative analysis of nanoparticle distribution in biological systems. Rare-earth nanoparticles are especially suited for multimodal imaging due to their superior upconversion properties, X-ray absorption capabilities, magnetic characteristics, tunable surface morphology, and biocompatibility. For instance, BaYbF5:Tm@BaGdF5:Yb,Tm core-shell nanocomposites exhibit multifunctionality, offering fluorescence/CT/MRI multimodal imaging capabilities. In vitro CT imaging using these core-shell structures shows better performance than conventional contrast agents such as iodine-based agents, providing improved contrast and longer circulation times, along with reduced toxicity.
Surface functionalization is a critical strategy for enhancing the CT imaging performance of nanoparticles. By modifying the surface properties of nanoparticles, researchers can improve their stability, biocompatibility, and contrast efficiency. For example, in dendrimer-gold nanoparticle systems, polyethylene glycol (PEG) modification has been shown to significantly improve the biocompatibility and circulation time of these materials in the body. Further functionalization, such as folic acid modification, enables nanoparticles to specifically target and accumulate in tumor sites, thereby enhancing CT signal contrast in tumor regions. Surface functionalization not only improves the contrast efficiency but also opens up the potential for targeted imaging, allowing for more precise and accurate diagnostics.
Dual-modal nanoprobes combine the strengths of both optical and CT imaging, offering more comprehensive diagnostic information. These probes typically consist of multiple functional components capable of generating both optical signals and X-ray attenuation signals, allowing for improved accuracy and resolution in imaging. For instance, combining rare-earth upconversion nanoparticles with CT contrast agents has proven to be an effective strategy for designing dual-modal probes. BaYbF5:Tm@BaGdF5:Yb,Tm core-shell nanoparticles are capable of fluorescence, CT, and MRI multimodal imaging. Compared to traditional contrast agents and other rare-earth-based multimodal contrast agents, these nanoparticles offer enhanced imaging performance, longer circulation times, and reduced toxicity. Their core-shell design not only improves upconversion luminescence efficiency but also serves as an excellent platform for surface functionalization.
Synergistic visualization strategies overcome the limitations of single imaging modalities by combining the advantages of different imaging techniques. One example is the fusion of optical molecular imaging with CT imaging. Researchers have successfully developed techniques using freeform optical technology to merge optical molecular images with CT scans of tumor lesions. By using reverse-engineering freeform optical reconstruction, they can discretize and reconstruct the optical channel surfaces of tumor tissues, significantly enhancing the quality of multimodal imaging fusion. Frequency-wavelength multiplexed optoacoustic tomography (FWMOT) is another synergistic strategy that improves signal-to-noise ratios by operating across multiple wavelengths. Unlike time-domain methods, FWMOT offers faster, multi-spectral operations and has shown superior performance in both model and in vivo experiments.
Real-time tracking and image-guided research are crucial applications of nanoparticles in biomedical research. CT imaging enables the tracking of nanoparticle distribution in vivo, providing a platform for real-time monitoring. For example, studies on NaLuF4:20%Gd3+ nanoparticles have demonstrated that these nanoparticles accumulate in various organs such as the lungs, liver, kidneys, and tumors within 48 hours of injection into tumor-bearing mice. The distribution characteristics can be tracked through CT imaging, offering valuable insights for treatment optimization and safety evaluation of nanoparticle metabolism. In image-guided research, nanoparticles serve not only as imaging agents but also as therapeutic agents or treatment guides. For instance, bismuth-based nanomaterials have shown potential in CT imaging-guided radiotherapy (RT) and photothermal therapy (PTT), demonstrating their capacity for integrated diagnostic and therapeutic applications.
Optimizing the signal-to-noise ratio (SNR) is a critical issue in multimodal imaging. In optical imaging, the use of upconversion nanoparticles significantly enhances the SNR. These nanoparticles can emit high-energy light (e.g., visible light) upon low-energy excitation (e.g., near-infrared light), and their anti-Stokes emission properties help reduce background autofluorescence, thereby improving the SNR. For CT imaging, nanoparticles made from high atomic number elements (such as gold, bismuth, tungsten) provide strong X-ray attenuation, thus enhancing CT signal contrast. Studies have shown that tungsten-based contrast agents exhibit higher CT values and greater image density compared to iodine-based agents at the same concentration, which directly contributes to improving the SNR. Furthermore, frequency-wavelength multiplexing strategies, such as FWMOT, offer new approaches to optimizing the SNR. By using pulsed illumination and frequency-domain multiplexing, FWMOT improves spectral measurements, providing superior SNR performance over time-domain methods.
Plasmonic nanostructures enhance optical signals through localized surface plasmon resonance (LSPR), with anisotropic structures such as gold nanorods and silver nanocubes showing significant electric field enhancement effects. These structures have demonstrated considerable potential in molecular imaging due to their strong optical enhancement properties. In addition, photonic nanostructures, such as photonic crystals and dielectric metasurfaces, provide precise control over light propagation, offering unique advantages in improving imaging resolution. The core-shell design allows for the simultaneous manipulation of both plasmonic and photonic properties. For example, gold nanorod-dielectric material core-shell structures can achieve multiple resonance modes, providing an ideal platform for multispectral imaging.
Multi-functional diagnostic nanoplatforms integrate various imaging modalities and therapeutic functions, achieving a unified diagnostic and therapeutic approach. Lanthanide-doped upconversion nanoplatforms can simultaneously perform fluorescence imaging, CT imaging, and magnetic resonance imaging (MRI), with fine-tuned energy levels enabling multicolor emission and high-resolution imaging. Hollow mesoporous silica nanocarriers can simultaneously load contrast agents and drugs, providing image-guided targeted therapy. Two-dimensional materials, such as molybdenum disulfide (MoS2), functionalized composite materials, combine photoacoustic imaging and photothermal therapy, demonstrating the synergistic effect of diagnosis and treatment. These platforms not only enhance diagnostic accuracy but also provide new possibilities for personalized therapy.
Environmentally responsive imaging probes are capable of intelligently adjusting their signal output in response to changes in the biological microenvironment, thereby enhancing imaging specificity and accuracy. pH-sensitive nanoprobes activate fluorescent signals in the acidic tumor microenvironment, improving tumor detection sensitivity. Reactive oxygen species (ROS)-responsive probes specifically react to molecules like hydrogen peroxide, enabling visualization of inflammatory sites. Enzyme-activated nanoprobes can release contrast agents under the action of specific proteases, enabling disease-specific imaging. Temperature-responsive polymer-encapsulated nanoprobes can switch signals based on temperature variations, providing a new tool for precise imaging.
Artificial intelligence (AI) technologies are significantly enhancing the data processing capabilities and resolution of nanoparticle-based imaging systems. Deep learning algorithms enable automatic recognition of nanoprobe distribution patterns within biological systems, facilitating early detection of minute lesions. Convolutional neural networks (CNNs) optimize multimodal image registration and fusion, improving the correlation between anatomical and functional information. Generative adversarial networks (GANs) can reconstruct high-quality images from low-dose CT data, reducing radiation exposure while maintaining diagnostic value. Reinforcement learning algorithms optimize imaging parameters in real time, adjusting to the optimal signal-to-noise ratio for enhanced image quality.
BOC Sciences offers comprehensive custom nanoprobe synthesis services, covering quantum dots, upconversion nanoparticles, gold nanostructures, and lanthanide-doped composite materials. We use colloidal chemistry to precisely control nanoparticle size and morphology and apply hot-injection technology to achieve the controlled preparation of monodisperse quantum dots. The microemulsion synthesis method is suitable for constructing various core-shell structures, ensuring uniform coating of the shell. Additionally, continuous ion layer adsorption reactions allow for atomic-level control of the shell layer, providing the foundation for the design and construction of multifunctional nanoprobes.
Table 1. Nanoparticles for Biomedical Applications Supported by BOC Sciences.
| Product Category | Description | Inquiry |
| Quantum Dots | Semiconductor nanocrystals with size-tunable fluorescence for biological imaging, offering high brightness and photostability. | Inquiry |
| Gold Nanoparticles | CT contrast agents with high X-ray attenuation, commonly used in cancer imaging and diagnostics. | Inquiry |
| Gold Nanoclusters | Small gold clusters with unique fluorescence properties, used in imaging due to their biocompatibility and stability. | Inquiry |
| Silver Nanoclusters | Silver nanoclusters for light scattering imaging, enabling real-time cell observation under confocal microscopy. | Inquiry |
| Upconversion Nanoparticles | Nanoparticles that absorb low-energy light and emit higher-energy light, ideal for deep tissue imaging with minimal autofluorescence. | Inquiry |
| Near-Infrared (NIR) Probes | Probes that emit light in the NIR range, providing deep tissue penetration for in vivo imaging applications. | Inquiry |
| Dual-Modal Nanoprobes | Nanoparticles combining optical and CT imaging for enhanced diagnostic accuracy and resolution. | Inquiry |
| Tungsten Oxide Nanoparticles | Tungsten-based nanoparticles for superior CT contrast, ideal for tumor imaging and diagnostic applications. | Inquiry |
| Rare-Earth Doped Nanocomposites | Nanocomposites with upconversion and X-ray absorption properties, suitable for multimodal imaging (CT, fluorescence, MRI). | Inquiry |
We are equipped with advanced characterization platforms, including high-resolution transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), and atomic force microscopy (AFM). X-ray diffraction (XRD) instruments precisely analyze crystal structures, and X-ray photoelectron spectroscopy (XPS) is used for surface chemical composition analysis. Our fluorescence spectroscopy system offers both steady-state and time-resolved measurements, while ultraviolet-visible-near infrared (UV-Vis-NIR) spectrophotometry provides comprehensive optical property analysis. Dynamic light scattering (DLS) and zeta potential analyzers evaluate the dispersion stability of nanoparticles, ensuring product quality meets research standards.
Table 2. Custom Nanoparticle Services for Imaging & Therapy.
| Service Name | Description | Inquiry |
| Nanoparticle Synthesis & Customization | Custom nanoparticle synthesis, tailored to specific size, morphology, and functionalization requirements. | Inquiry |
| Nanoparticle Surface Functionalization | Surface modification (e.g., PEGylation, antibody conjugation) to enhance biocompatibility and targeting. | Inquiry |
| In Vivo Nanoparticle Tracking | Real-time monitoring of nanoparticle distribution and metabolism in small animal models via imaging. | Inquiry |
| Nanoparticle Targeted Drug Delivery | Development of nanoparticle-based systems for targeted drug delivery to specific tissues or cells. | Inquiry |
| Nanoparticle Biocompatibility Testing | Testing nanoparticles for cytotoxicity and immune response to ensure safety for in vivo applications. | Inquiry |
We have developed advanced nanoparticle surface modification techniques, including silanization, thiolation, and phospholipid modification. PEG modification enhances nanoparticle biocompatibility, while carboxyl, amino, and thiol functionalizations provide reactive sites for subsequent bioconjugation. We use the streptavidin-biotin system for high-affinity conjugation and click chemistry for directional immobilization of biomolecules. Targeted molecules, such as antibodies, peptides, and nucleic acid aptamers, can be precisely modified onto the nanoparticle surface using various chemical bonding methods, ensuring targeted functionality.
BOC Sciences is committed to providing comprehensive technical support to researchers, covering the entire process from experimental design to results translation. We offer material selection consulting based on specific application requirements and biological system characteristics, recommending the most suitable nanoprobe solutions. Our custom services are designed to meet specific research goals, optimizing nanoparticle structure, surface chemistry, synthesis routes, and characterization protocols. Our professional technical team provides application guidance and result analysis support, ensuring the successful implementation of research projects.
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