The effect of the size of gold nanoparticle contrast agents on CT imaging of the gastrointestinal tract and inflammatory bowel disease.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD). CT imaging with contrast agents is commonly used for visualizing the gastrointestinal (GI) tract in UC patients. CT is a common imaging modality for evaluating IBD, especially in patients with acute abdominal pain presenting to emergency departments. CT's major limitation lies in its lack of specificity for imaging UC, as the commonly used agents are not well-suited for inflamed areas. Recent studies gastrointestinal tract (GIT) in UC. Further systemic research is needed to explore novel contrast agents that can specifically image disease processes in this disease setting.

Novel Combination Treatment for Melanoma: FLASH Radiotherapy and Immunotherapy Delivered by a Radiopaque and Radiation Responsive Hydrogel.

Immunotherapies have become the standard treatment for melanoma. To further improve patient responses, combinations of immunotherapies and radiotherapy (RT) are being studied, since radiotherapies can potentially provide additional immune stimulation, in addition to direct antitumor effects. FLASH-RT is a novel, ultrahigh dose rate, radiation delivery approach, with the potential of at least equivalent tumor control efficacy and reduced damage to healthy tissue. However, the effects of combining FLASH-RT and immunotherapy have not been extensively studied in melanoma. Toll-like receptor (TLR) agonists, such as imiquimod (IMQ), are potent immunostimulatory agents, although their utility is limited due to poor solubility and systemic side effects. We therefore developed a novel combination therapy for melanoma consisting of IMQ delivered to the tumor via a radiopaque and radiation responsive hydrogel combined with FLASH-RT. We found that FLASH was able to effectively stimulate IMQ release from the hydrogel. In addition, we found that the combination of FLASH and released IMQ resulted in synergistic melanoma cell killing in vitro. The combination therapy reduced tumor growth compared to controls, enhanced survival, and resulted in remarkable enhancements in certain tumor cytokine levels. CT imaging allowed the hydrogel to be monitored in vivo. In addition, no adverse effects of the treatment were observed. Overall, this IMQ-gel and FLASH-RT combination may have potential as an improved treatment for melanoma and indicates that the interactions of FLASH-RT and TLR agonists merit further study.

Renally Excretable Silver Telluride Nanoparticles as Contrast Agents for X-ray Imaging.

The use of nanoparticles in the biomedical field has gained much attention due to their applications in biomedical imaging, drug delivery, and therapeutics. Silver telluride nanoparticles (Ag2Te NPs) have been recently shown to be highly effective computed tomography (CT) and dual-energy mammography contrast agents with good stability and biocompatibility, as well as to have potential for many other biomedical purposes. Despite their numerous advantageous properties for diagnosis and treatment of disease, the clinical translation of Ag2Te NPs is dependent on achieving high levels of excretion, a limitation for many nanoparticle types. In this work, we have synthesized and characterized a library of Ag2Te NPs and identified conditions that led to 3 nm core size and were renally excretable. We found that these nanoparticles have good biocompatibility, strong X-ray contrast generation, and rapid renal clearance. Our CT data suggest that renal elimination of nanoparticles occurred within 2 h of administration. Moreover, biodistribution data indicate that 93% of the injected dose (%ID) has been excreted from the main organs in 24 h, 95% ID in 7 days, and 97% ID in 28 days with no signs of acute toxicity in the tissues studied under histological analysis. To our knowledge, this renal clearance is the best reported for Ag2Te NP, while being comparable to the highest renal clearance reported for any type of nanoparticle. Together, the results herein presented suggest the use of GSH-Ag2Te NPs as an X-ray contrast agent with the potential to be clinically translated in the future.

Ytterbium Nanoparticle Contrast Agents for Conventional and Spectral Photon-Counting CT and Their Applications for Hydrogel Imaging.

Significant work has been done to develop nanoparticle contrast agents for computed tomography (CT), with a focus on identifying safer and more effective formulations. Contrast agents for spectral photon-counting computed tomography (SPCCT), a fast-growing imaging modality derived from conventional CT, have also recently gained considerable attention. In this study, we explored the synthesis of ultrasmall ytterbium nanoparticles (YbNP) and demonstrated that, potentially, they can be used as conventional CT and SPCCT contrast agents. These nanoparticles were tested in vitro for their cytotoxicity and contrast-generating properties with a variety of imaging systems. When scanned with conventional CT and SPCCT at clinically relevant energies, YbNP are significantly more attenuating than gold nanoparticles (AuNP), the contrast agents that have been most well studied. Furthermore, YbNP were studied for their potential application for labeling and monitoring hydrogels. The presence of the YbNP payload in hydrogels allowed for hydrogel localization and tracking in vivo. Additionally, the in vivo imaging results revealed that YbNP generate higher contrast when compared to AuNP used as a label. In summary, this is the first research study to examine ultrasmall YbNP as conventional CT and SPCCT contrast agents, as well as using them in a hydrogel system to make it radiopaque. These findings underscore YbNP's utility as CT and SPCCT contrast agents, as well as their potential for tracking hydrogels in vivo.

Silver chalcogenide nanoparticles: a review of their biomedical applications.

Silver chalcogenide (Ag2X, where X = S, Se, or Te) nanoparticles have been extensively investigated for their applications in electronics but have only recently been explored for biomedical applications. In the past 10 years, Ag2X, primarily silver sulfides at first, have become of great importance as quantum dots, since they not only possess excellent deep tissue imaging properties in the near-infrared regions I and II, but also have low toxicities. Their appealing properties have led to numerous recent developments of Ag2X for biomedical applications. Furthermore, Ag2X have been discovered in the past 2-3 years to be potent X-ray contrast agents, adding to the numerous biomedical uses of these nanoparticles. In this review, we discuss the most recent advances in silver chalcogenide nanoparticle use in areas such as bio-imaging, theranostics, and biosensors. Moreover, we examine the advances in synthetic approaches for these nanoparticles, which include aqueous and organic syntheses routes. Finally, we discuss the advantages and current limitations in the use of silver chalcogenides for different biomedical applications and their potential for advancement and expansions in use.

Silver telluride nanoparticles as biocompatible and enhanced contrast agents for X-ray imaging: an in vivo breast cancer screening study.

Silver sulfide nanoparticles (Ag2S NPs) have gained considerable interest in the biomedical field due to their photothermal ablation enhancement, near-infrared fluorescence properties, low toxicity levels, and multi-imaging capabilities. Silver telluride nanoparticles (Ag2Te NPs) have similar properties to Ag2S NPs, should also be stable due to an extremely low solubility product and should generate greater X-ray contrast since tellurium is significantly more attenuating than sulfur at diagnostic X-ray energies. Despite these attractive properties, Ag2Te NPs have only been studied in vivo once and at a low dose (2 mg Ag per kg). Herein, for the first time, Ag2Te NPs' properties and their application in the biomedical field were studied in vivo in the setting requiring the highest nanoparticle doses of all biomedical applications, i.e. X-ray imaging. Ag2Te NPs were shown to be stable, biocompatible (no acute toxicity observed in the cell lines studied or in vivo), and generated higher contrast, compared to controls, in the two X-ray imaging techniques studied: computed tomography (CT) and dual-energy mammography (DEM). In summary, this is the first study where Ag2Te NPs were explored in vivo at a high dose. Our findings suggest that Ag2Te NPs provide strong X-ray contrast while exhibiting excellent biocompatibility. These results highlight the potential use of Ag2Te NPs in the biomedical field and as X-ray contrast agents for breast cancer screening.

Precision targeting of bacterial pathogen via bi-functional nanozyme activated by biofilm microenvironment.

Human dental caries is an intractable biofilm-associated disease caused by microbial interactions and dietary sugars on the host's teeth. Commensal bacteria help control opportunistic pathogens via bioactive products such as hydrogen peroxide (H2O2). However, high-sugar consumption disrupts homeostasis and promotes pathogen accumulation in acidic biofilms that cause tooth-decay. Here, we exploit the pathological (sugar-rich/acidic) conditions using a nanohybrid system to increase intrinsic H2O2 production and trigger pH-dependent reactive oxygen species (ROS) generation for efficient biofilm virulence targeting. The nanohybrid contains glucose-oxidase that catalyzes glucose present in biofilms to increase intrinsic H2O2, which is converted by iron oxide nanoparticles with peroxidase-like activity into ROS in acidic pH. Notably, it selectively kills Streptococcus mutans (pathogen) without affecting Streptococcus oralis (commensal) via preferential pathogen-binding and in situ ROS generation. Furthermore, nanohybrid treatments potently reduced dental caries in a rodent model. Compared to chlorhexidine (positive-control), which disrupted oral microbiota diversity, the nanohybrid had significant higher efficacy without affecting soft-tissues and the oral-gastrointestinal microbiomes, while modulating dental health-associated microbial activity in vivo. The data reveal therapeutic precision of a bi-functional hybrid nanozyme against a biofilm-related disease in a controlled-manner activated by pathological conditions.

Nanoparticle contrast agents for X-ray imaging applications.

X-ray imaging is the most widely used diagnostic imaging method in modern medicine and several advanced forms of this technology have recently emerged. Iodinated molecules and barium sulfate suspensions are clinically approved X-ray contrast agents and are widely used. However, these existing contrast agents provide limited information, are suboptimal for new X-ray imaging techniques and are developing safety concerns. Thus, over the past 15 years, there has been a rapid growth in the development of nanoparticles as X-ray contrast agents. Nanoparticles have several desirable features such as high contrast payloads, the potential for long circulation times, and tunable physicochemical properties. Nanoparticles have also been used in a range of biomedical applications such as disease treatment, targeted imaging, and cell tracking. In this review, we discuss the principles behind X-ray contrast generation and introduce new types of X-ray imaging modalities, as well as potential elements and chemical compositions that are suitable for novel contrast agent development. We focus on the progress in nanoparticle X-ray contrast agents developed to be renally clearable, long circulating, theranostic, targeted, or for cell tracking. We feature agents that are used in conjunction with the newly developed multi-energy computed tomography and mammographic imaging technologies. Finally, we offer perspectives on current limitations and emerging research topics as well as expectations for the future development of the field. This article is categorized under: Diagnostic Tools > in vivo Nanodiagnostics and Imaging Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.