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Complex metal nanostructures represent an exceptional category of materials characterized by distinct morphologies and physicochemical properties. Nanostructures with shape anisotropies, such as nanorods, nanostars, nanocages, and nanoprisms, are particularly appealing due to their tunable surface plasmon resonances, controllable surface chemistries, and effective targeting capabilities. These complex nanostructures can absorb light in the near-infrared, enabling noteworthy applications in nanomedicine, molecular imaging, and biology. The engineering of targeting abilities through surface modifications involving ligands, antibodies, peptides, and other agents potentiates their effects. Recent years have witnessed the development of innovative structures with diverse compositions, expanding their applications in biomedicine. These applications encompass targeted imaging, surface-enhanced Raman spectroscopy, near-infrared II imaging, catalytic therapy, photothermal therapy, and cancer treatment. This review seeks to provide the nanomedicine community with a thorough and informative overview of the evolving landscape of complex metal nanoparticle research, with a specific emphasis on their roles in imaging, cancer therapy, infectious diseases, and biofilm treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Diagnostic Tools > Diagnostic Nanodevices.
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Nanopartículas del Metal , Nanomedicina , Neoplasias , Humanos , Animales , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Nanoestructuras/química , RatonesRESUMEN
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.
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Objectives. Evaluate the reproducibility, temperature tolerance, and radiation dose requirements of spectral CT thermometry in tissue-mimicking phantoms to establish its utility for non-invasive temperature monitoring of thermal ablations.Methods. Three liver mimicking phantoms embedded with temperature sensors were individually scanned with a dual-layer spectral CT at different radiation dose levels during heating (35 °C-80 °C). Physical density maps were reconstructed from spectral results using varying reconstruction parameters. Thermal volumetric expansion was then measured at each temperature sensor every 5 °C in order to establish a correlation between physical density and temperature. Linear regressions were applied based on thermal volumetric expansion for each phantom, and coefficient of variation for fit parameters was calculated to characterize reproducibility of spectral CT thermometry. Additionally, temperature tolerance was determined to evaluate effects of acquisition and reconstruction parameters. The resulting minimum radiation dose to meet the clinical temperature accuracy requirement was determined for each slice thickness with and without additional denoising.Results. Thermal volumetric expansion was robustly replicated in all three phantoms, with a correlation coefficient variation of only 0.43%. Similarly, the coefficient of variation for the slope and intercept were 9.6% and 0.08%, respectively, indicating reproducibility of the spectral CT thermometry. Temperature tolerance ranged from 2 °C to 23 °C, decreasing with increased radiation dose, slice thickness, and iterative reconstruction level. To meet the clinical requirement for temperature tolerance, the minimum required radiation dose ranged from 20, 30, and 57 mGy for slice thickness of 2, 3, and 5 mm, respectively, but was reduced to 2 mGy with additional denoising.Conclusions. Spectral CT thermometry demonstrated reproducibility across three liver-mimicking phantoms and illustrated the clinical requirement for temperature tolerance can be met for different slice thicknesses. The reproducibility and temperature accuracy of spectral CT thermometry enable its clinical application for non-invasive temperature monitoring of thermal ablation.
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Termometría , Reproducibilidad de los Resultados , Termometría/métodos , Temperatura , Hígado/diagnóstico por imagen , Hígado/cirugía , Fantasmas de Imagen , Tomografía Computarizada por Rayos XRESUMEN
Fungal pathogens have been designated by the World Health Organization as microbial threats of the highest priority for global health. It remains a major challenge to improve antifungal efficacy at the site of infection while avoiding off-target effects, fungal spreading, and drug tolerance. Here, a nanozyme-based microrobotic platform is developed that directs localized catalysis to the infection site with microscale precision to achieve targeted and rapid fungal killing. Using electromagnetic field frequency modulation and fine-scale spatiotemporal control, structured iron oxide nanozyme assemblies are formed that display tunable dynamic shape transformation and catalysis activation. The catalytic activity varies depending on the motion, velocity, and shape providing controllable reactive oxygen species (ROS) generation. Unexpectedly, nanozyme assemblies bind avidly to fungal (Candida albicans) surfaces to enable concentrated accumulation and targeted ROS-mediated killing in situ. By exploiting these tunable properties and selective binding to fungi, localized antifungal activity is achieved using in vivo-like cell spheroid and animal tissue infection models. Structured nanozyme assemblies are directed to Candida-infected sites using programmable algorithms to perform precisely guided spatial targeting and on-site catalysis resulting in fungal eradication within 10 min. This nanozyme-based microrobotics approach provides a uniquely effective and targeted therapeutic modality for pathogen elimination at the infection site.
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Antifúngicos , Micosis , Animales , Antifúngicos/química , Antifúngicos/metabolismo , Antifúngicos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Candida albicans/metabolismo , Modelos AnimalesRESUMEN
Silver sulfide nanoparticles (Ag2S-NP) hold promise for various optical-based biomedical applications, such as near-infrared fluorescence (NIRF) imaging, photoacoustics (PA), and photothermal therapy (PTT). However, their NIR absorbance is relatively low, and previous formulations are synthesized using toxic precursors under harsh conditions and are not effectively cleared due to their large size. Herein, sub-5 nm Ag2S-NP are synthesized and encapsulated in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses are conducted using biocompatible, aqueous reagents under ambient conditions. The encapsulation of Ag2S-NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and PTT effects. AgPCPP nanoparticles exhibit potent contrast properties suitable for PA and NIRF imaging, as well as for computed tomography (CT). Furthermore, AgPCPP nanoparticles readily improve the conspicuity of breast tumors in vivo. Under NIR laser irradiation, AgPCPP nanoparticles significantly reduce breast tumor growth, leading to prolonged survival compared to free Ag2S-NP. Over time, AgPCPP retention in tissues gradually decreases, without any signs of acute toxicity, providing strong evidence of their safety and biodegradability. Therefore, AgPCPP may serve as a "one-for-all" theranostic agent that degrades into small components for excretion after fulfilling diagnostic and therapeutic tasks, offering good prospects for clinical translation.
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Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Neoplasias de la Mama/terapia , Fototerapia/métodos , Línea Celular Tumoral , Nanomedicina Teranóstica/métodos , PolímerosRESUMEN
Silver sulfide nanoparticles (Ag 2 S-NP) have been proposed for various optical-based biomedical applications, such as near-infrared fluorescence (NIRF) imaging, photoacoustics (PA) and photothermal therapy (PTT). However, their absorbance is relatively low in the NIR window used in these applications, and previous formulations were synthesized using toxic precursors under harsh conditions and have clearance issues due to their large size. Herein, we synthesized sub-5 nm Ag 2 S-NP and encapsulated them in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses were conducted using biocompatible reagents in the aqueous phase and under ambient conditions. We found that the encapsulation of Ag 2 S-NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and photothermal heating effects. We therefore found that AgPCPP have potent contrast properties for PA and NIRF imaging, as well as for computed tomography (CT). We demonstrated the applicability of AgPCPP nanoparticles as a multimodal imaging probe that readily improves the conspicuity of breast tumors in vivo . PTT was performed using AgPCPP with NIR laser irradiation, which led to significant reduction in breast tumor growth and prolonged survival compared to free Ag 2 S-NP. Lastly, we observed a gradual decrease in AgPCPP retention in tissues over time with no signs of acute toxicity, thus providing strong evidence of safety and biodegradability. Therefore, AgPCPP may serve as a "one-for-all" theranostic agent that degrades into small components for excretion once the diagnostic and therapeutic tasks are fulfilled, thus providing good prospects for translation to clinical use.
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Ultrasmall silver sulfide nanoparticles (Ag 2 S-NP) have been identified as promising contrast agents for a number of modalities and in particular for dual-energy mammography. These Ag 2 S-NP have demonstrated marked advantages over clinically available agents with the ability to generate higher contrast with high biocompatibility. However, current synthesis methods are low-throughput and highly time-intensive, limiting the possibility of large animal studies or eventual clinical use of this potential imaging agent. We herein report the use of a scalable silicon microfluidic system (SSMS) for the large-scale synthesis of Ag 2 S-NP. Using SSMS chips with 1 channel, 10 parallelized channels, and 256 parallelized channels, we determined that the Ag 2 S-NP produced were of similar quality as measured by core size, concentration, UV-visible spectrometry, and in vitro contrast generation. Moreover, by combining parallelized chips with increasing reagent concentration, we were able to increase output by an overall factor of 3,400. We also found that in vivo imaging contrast generation was consistent across synthesis methods and confirmed renal clearance of the ultrasmall nanoparticles. Finally, we found best-in-class clearance of the Ag 2 S-NP occurred within 24 hours. These studies have identified a promising method for the large-scale production of Ag 2 S-NP, paving the way for eventual clinical translation.
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Medical imaging, which empowers the detection of physiological and pathological processes within living subjects, has a vital role in both preclinical and clinical diagnostics. Contrast agents are often needed to accompany anatomical data with functional information or to provide phenotyping of the disease in question. Many newly emerging contrast agents are based on nanomaterials as their high payloads, unique physicochemical properties, improved sensitivity and multimodality capacity are highly desired for many advanced forms of bioimaging techniques and applications. Here, we review the developments in the field of nanomaterial-based contrast agents. We outline important nanomaterial design considerations and discuss the effect on their physicochemical attributes, contrast properties and biological behaviour. We also describe commonly used approaches for formulating, functionalizing and characterizing these nanomaterials. Key applications are highlighted by categorizing nanomaterials on the basis of their X-ray, magnetic, nuclear, optical and/or photoacoustic contrast properties. Finally, we offer our perspectives on current challenges and emerging research topics as well as expectations for future advancements in the field.
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CT systems equipped with photon-counting detectors (PCDs), referred to as photon-counting CT (PCCT), are beginning to change imaging in several subspecialties, such as cardiac, vascular, thoracic, and musculoskeletal radiology. Evidence has been building in the literature underpinning the many advantages of PCCT for different clinical applications. These benefits derive from the distinct features of PCDs, which are made of semiconductor materials capable of converting photons directly into electric signal. PCCT advancements include, among the most important, improved spatial resolution, noise reduction, and spectral properties. PCCT spatial resolution on the order of 0.25 mm allows for the improved visualization of small structures (eg, small vessels, arterial walls, distal bronchi, and bone trabeculations) and their pathologies, as well as the identification of previously undetectable anomalies. In addition, blooming artifacts from calcifications, stents, and other dense structures are reduced. The benefits of the spectral capabilities of PCCT are broad and include reducing radiation and contrast material dose for patients. In addition, multiple types of information can be extracted from a single data set (ie, multiparametric imaging), including quantitative data often regarded as surrogates of functional information (eg, lung perfusion). PCCT also allows for a novel type of CT imaging, K-edge imaging. This technique, combined with new contrast materials specifically designed for this modality, opens the door to new applications for imaging in the future.
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Arterias , Tomografía Computarizada por Rayos X , Humanos , Artefactos , Bronquios , Medios de ContrasteRESUMEN
Objectives: Evaluate the reproducibility, temperature sensitivity, and radiation dose requirements of spectral CT thermometry in tissue-mimicking phantoms to establish its utility for non-invasive temperature monitoring of thermal ablations. Materials and Methods: Three liver mimicking phantoms embedded with temperature sensors were individually scanned with a dual-layer spectral CT at different radiation dose levels during heating and cooling (35 to 80 °C). Physical density maps were reconstructed from spectral results using a range of reconstruction parameters. Thermal volumetric expansion was then measured at each temperature sensor every 5°C in order to establish a correlation between physical density and temperature. Linear regressions were applied based on thermal volumetric expansion for each phantom, and coefficient of variation for fit parameters was calculated to characterize reproducibility of spectral CT thermometry. Additionally, temperature sensitivity was determined to evaluate the effect of acquisition parameters, reconstruction parameters, and image denoising. The resulting minimum radiation dose to meet the clinical temperature sensitivity requirement was determined for each slice thickness, both with and without additional denoising. Results: Thermal volumetric expansion was robustly replicated in all three phantoms, with a correlation coefficient variation of only 0.43%. Similarly, the coefficient of variation for the slope and intercept were 9.6% and 0.08%, respectively, indicating reproducibility of the spectral CT thermometry. Temperature sensitivity ranged from 2 to 23 °C, decreasing with increased radiation dose, slice thickness, and iterative reconstruction level. To meet the clinical requirement for temperature sensitivity, the minimum required radiation dose ranged from 20, 30, and 57 mGy for slice thickness of 2, 3, and 5 mm, respectively, but was reduced to 2 mGy with additional denoising. Conclusions: Spectral CT thermometry demonstrated reproducibility across three liver-mimicking phantoms and illustrated the clinical requirement for temperature sensitivity can be met for different slice thicknesses. Moreover, additional denoising enables the use of more clinically relevant radiation doses, facilitating the clinical translation of spectral CT thermometry. The reproducibility and temperature accuracy of spectral CT thermometry enable its clinical application for non-invasive temperature monitoring of thermal ablation.
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Dental caries is the most common human disease caused by oral biofilms despite the widespread use of fluoride as the primary anticaries agent. Recently, an FDA-approved iron oxide nanoparticle (ferumoxytol, Fer) has shown to kill and degrade caries-causing biofilms through catalytic activation of hydrogen peroxide. However, Fer cannot interfere with enamel acid demineralization. Here, we show notable synergy when Fer is combined with stannous fluoride (SnF2), markedly inhibiting both biofilm accumulation and enamel damage more effectively than either alone. Unexpectedly, we discover that the stability of SnF2 is enhanced when mixed with Fer in aqueous solutions while increasing catalytic activity of Fer without any additives. Notably, Fer in combination with SnF2 is exceptionally effective in controlling dental caries in vivo, even at four times lower concentrations, without adverse effects on host tissues or oral microbiome. Our results reveal a potent therapeutic synergism using approved agents while providing facile SnF2 stabilization, to prevent a widespread oral disease with reduced fluoride exposure.
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Caries Dental , Fluoruros de Estaño , Humanos , Fluoruros de Estaño/farmacología , Fluoruros de Estaño/uso terapéutico , Fluoruros/farmacología , Caries Dental/prevención & control , Biopelículas , Fluoruro de Sodio/farmacologíaRESUMEN
Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we described a complex structure of a dextran-coated gold-in-gold cage nanoparticle that enabled photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser could selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observed a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections, respectively. These effects were over 100 times greater than those seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We concluded that photothermal ablation using theranostic nanoparticles is a rapid, precise, and nontoxic method to detect and treat biofilm-associated infections.
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Nanopartículas , Técnicas Fotoacústicas , Infección de Heridas , Animales , Ratones , Antibacterianos , Biopelículas , Oro/farmacología , Oro/química , Nanopartículas/química , Medicina de PrecisiónRESUMEN
Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we describe a unique structure of dextran coated gold in a gold cage nanoparticle that enables photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser can selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observe a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections respectively. These effects were over 100 times greater than that seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We conclude that photothermal ablation using theranostic nanoparticles is a rapid, precise, and non-toxic method to detect and treat biofilm-associated infections.
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A key process in the development of atherosclerotic plaques is the recruitment of monocytes into the artery wall. Using spectral photon-counting computed tomography we examine whether monocyte deposition within the artery wall of ApoE-/- mouse can be detected. Primary mouse monocytes were labelled by incubating them with 15 nm gold nanoparticles coated with 11-mercaptoundecanoic acid The monocyte uptake of the particle was confirmed by electron microscopy of the cells before injection into 6-week-old apolipoprotein E deficient (ApoE-/-) mouse that had been fed with the Western diet for 10 weeks. Four days following injection, the mouse was sacrificed and imaged using a MARS spectral photon counting computed tomography scanner with a spectral range of 7 to 120 KeV with five energy bins. Imaging analysis showed the presence of X-ray dense material within the mouse aortic arch which was consistent with the spectral characteristic of gold rather than calcium. The imaging is interpreted as showing the deposition of gold nanoparticles containing monocytes within the mouse aorta. The results of our study determined that spectral photon-counting computed tomography could provide quantitative information about gold nanoparticles labelled monocytes in voxels of 90 × 90 × 90 µm3. The imaging was consistent with previous micro-CT and electron microscopy of mice using the same nanoparticles. This study demonstrates that spectral photon-counting computed tomography, using a MARS small bore scanner, can detect a fundamental atherogenic process within mouse models of atherogenesis. The present study demonstrates the feasibility of spectral photon-counting computed tomography as an emerging molecular imaging modality to detect atherosclerotic disease.
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The activation of phagocytic cells is a hallmark of many neurological diseases. Imaging them in their 3-dimensional cerebral environment over time is crucial to better understand their role in disease pathogenesis and to monitor their potential therapeutic effects. Phagocytic cells have the ability to internalize metal-based contrast agents both in vitro and in vivo and can thus be tracked by magnetic resonance imaging (MRI) or computed tomography (CT). In this review article, we summarize the different labelling strategies, contrast agents, and in vivo imaging modalities that can be used to monitor cells with phagocytic activity in the central nervous system using MRI and CT, with a focus on clinical applications. Metal-based nanoparticle contrast agents such as gadolinium, gold and iron are ideal candidates for these applications as they have favourable magnetic and/or radiopaque properties and can be fine-tuned for optimal uptake by phagocytic cells. However, they also come with downsides due to their potential toxicity, especially in the brain where they might accumulate. We therefore conclude our review by discussing the pitfalls, safety and potential for clinical translation of these metal-based neuroimaging techniques. Early results in patients with neuropathologies such as multiple sclerosis, stroke, trauma, cerebral aneurysm and glioblastoma are promising. If the challenges represented by safety issues are overcome, phagocytic cells imaging will be a very valuable tool for studying and understanding the inflammatory response and evaluating treatments that aim at mitigating this response in patients with neurological diseases.
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Medios de Contraste , Enfermedades del Sistema Nervioso , Humanos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X , Gadolinio , Fagocitos , Enfermedades del Sistema Nervioso/diagnóstico por imagenRESUMEN
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.
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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.
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Medios de Contraste , Nanopartículas del Metal , Oro , Hidrogeles , Nanopartículas del Metal/toxicidad , Fantasmas de Imagen , Fotones , Tomografía Computarizada por Rayos X/métodos , IterbioRESUMEN
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.
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Medios de Contraste , Nanopartículas , Plata , Distribución Tisular , Rayos XRESUMEN
Ferumoxytol is an intravenous iron oxide nanoparticle formulation that has been approved by the U.S. Food and Drug Administration (FDA) for treating anemia in patients with chronic kidney disease. In recent years, ferumoxytol has also been demonstrated to have potential for many additional biomedical applications due to its excellent inherent physical properties, such as superparamagnetism, biocatalytic activity, and immunomodulatory behavior. With good safety and clearance profiles, ferumoxytol has been extensively utilized in both preclinical and clinical studies. Here, we first introduce the medical needs and the value of current iron oxide nanoparticle formulations in the market. We then focus on ferumoxytol nanoparticles and their physicochemical, diagnostic, and therapeutic properties. We include examples describing their use in various biomedical applications, including magnetic resonance imaging (MRI), multimodality imaging, iron deficiency treatment, immunotherapy, microbial biofilm treatment and drug delivery. Finally, we provide a brief conclusion and offer our perspectives on the current limitations and emerging applications of ferumoxytol in biomedicine. Overall, this review provides a comprehensive summary of the developments of ferumoxytol as an agent with diagnostic, therapeutic, and theranostic functionalities.
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Reposicionamiento de Medicamentos , Óxido Ferrosoférrico/uso terapéutico , Nanopartículas del Metal/uso terapéutico , Animales , Antineoplásicos/uso terapéutico , Aprobación de Drogas , Humanos , Hierro , Deficiencias de Hierro/tratamiento farmacológico , Imagen por Resonancia Magnética , Nanopartículas del Metal/química , Medicina de Precisión , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Gold nanoparticles (AuNP) are well-established contrast agents in computed tomography (CT) and photoacoustic imaging (PAI). A wide variety of AuNP sizes, shapes, and coatings have been reported for these applications. However, for clinical translation, AuNP should be excretable to avoid long-term accumulation and possible side effects. Sub-5 nm AuNP have the benefit to be excretable through kidney filtration, therefore their loading in biodegradable nanogels holds promise to result in contrast agents that have long circulation times in the vasculature and subsequent biodegradation for excretion. Polyphosphazenes are intrinsically biodegradable polymers capable of forming nanogels with high payloads, and to release their payloads upon degradation. The significant development in polyphosphazenes that have tailored degradation kinetics, and their formulation with drugs or contrast agents, has shown potential as a biodegradable platform for imaging vasculature and endogenous molecules, by combination of CT and PA modalities. Therefore, we herein present methods for the formulation of AuNP assemblies loaded in nanogels composed of biodegradable polyphosphazenes, with a size range from 50 to 200 nm. We describe protocols for their characterization by UV-vis spectroscopy, Fourier-transform infrared spectroscopy, various microscopy techniques, elemental quantification by induced coupling plasma optical emission spectroscopy and contrast production in both CT and PAI. Finally, we detail the methods to investigate their effect on cells, distribution in cells and imaging properties for detection of endogenous molecules.