Nanoparticle Contrast Research Articles

Towards the clinical translation of a silver sulfide nanoparticle contrast agent: large scale production with a highly parallelized microfluidic chip.

Ultrasmall silver sulfide nanoparticles (Ag2S-NP) have been identified as promising contrast agents for a number of modalities and in particular for dual-energy mammography. These Ag2S-NP have demonstrated marked advantages over clinically available agents with the ability to generate higher contrast with high biocompatibility. However, current synthesis methods for inorganic nanoparticles 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 Ag2S-NP. Ag2S-NP produced using this system were compared to bulk synthesis and a commercially available microfluidic device through characterization, contrast generation, in vivo imaging, and clearance profiles. Using SSMS chips with 1 channel, 10 parallelized channels, and 256 parallelized channels, we determined that the Ag2S-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 5,100. 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 Ag2S-NP occurred within 24h. These studies have identified a promising method for the large-scale production of Ag2S-NP, paving the way for eventual clinical translation.

Novel intravascular tantalum oxide-based contrast agent achieves improved vascular contrast enhancement and conspicuity compared to Iopamidol in an animal multiphase CT protocol

BackgroundTo assess thoracic vascular computed tomography (CT) contrast enhancement of a novel intravenous tantalum oxide nanoparticle contrast agent (carboxybetaine zwitterionic tantalum oxide, TaCZ) compared to a conventional iodinated contrast agent (Iopamidol) in a rabbit multiphase protocol.MethodsFive rabbits were scanned inside a human-torso-sized encasement on a clinical CT system at various scan delays after intravenous injection of 540 mg element (Ta or I) per kg of bodyweight of TaCZ or Iopamidol. Net contrast enhancement of various arteries and veins, as well as image noise, were measured. Randomized scan series were reviewed by three independent readers on a clinical workstation and assessed for vascular conspicuity and image artifacts on 5-point Likert scales.ResultsOverall, net vascular contrast enhancement achieved with TaCZ was superior to Iopamidol (p ≤ 0.036 with the exception of the inferior vena cava at 6 s (p = 0.131). Vascular contrast enhancement achieved with TaCZ at delays of 6 s, 40 s, and 75 s was superior to optimum achieved Iopamidol contrast enhancement at 6 s (p ≤ 0.036. Vascular conspicuity was higher for TaCZ in 269 of 300 (89.7%) arterial and 269 of 300 (89.7%) venous vessel assessments, respectively (p ≤ 0.005), with substantial inter-reader reliability (κ = 0.61; p < 0.001) and strong positive monotonic correlation between conspicuity scores and contrast enhancement measurements (ρ = 0.828; p < 0.001).ConclusionTaCZ provides absolute and relative contrast advantages compared to Iopamidol for improved visualization of thoracic arteries and veins in a multiphase CT protocol.Relevance statementThe tantalum-oxide nanoparticle is an experimental intravenous CT contrast agent with superior cardiovascular and venous contrast capacity per injected elemental mass in an animal model, providing improved maximum contrast enhancement and prolonged contrast conspicuity. Further translational research on promising high-Z and nanoparticle contrast agents is warranted.Key PointsThere have been no major advancements in intravenous CT contrast agents over decades.Iodinated CT contrast agents require optimal timing for angiography and phlebography.Tantalum-oxide demonstrated increased CT attenuation per elemental mass compared to Iopamidol.Nanoparticle contrast agent design facilitates prolonged vascular conspicuity.Graphical

Retracted] Application of a novel targeting nanoparticle contrast agent combined with magnetic resonance imaging in the diagnosis of intraductal papillary mucinous neoplasm.

[This retracts the article DOI: 10.3892/etm.2018.6349.].

Clinical applications, safety profiles, and future developments of contrast agents in modern radiology: A comprehensive review

AbstractContrast agents have transformed the field of medical imaging, significantly enhancing the visualisation of internal structures and improving diagnostic accuracy across X‐rays, computed tomography, magnetic resonance imaging (MRI), and ultrasound. This review explores the historical development, physicochemical properties, and mechanisms of action of iodinated, gadolinium‐based, barium sulfate, microbubble, and nanoparticle contrast agents. It highlights key advancements, including the transition from high‐osmolar to low‐ and iso‐osmolar iodinated agents, the integration of gadolinium in MRI, and the innovative use of microbubbles and nanoparticles. The review critically examines the safety profiles and adverse reactions of these contrast agents, categorising them into hypersensitivity and physiological reactions. It outlines risk factors, common misconceptions, and management strategies for adverse reactions, emphasising the importance of personalised approaches in clinical practice. Additionally, it delves into broader implications, including ethical considerations, environmental impact, and global accessibility of contrast media. The review also discusses technological advancements such as targeted contrast agents and the integration of artificial intelligence to optimise contrast dosage. By synthesising current knowledge and emerging trends, this review underscores the pivotal role of contrast agents in advancing medical imaging. It aims to equip clinicians, researchers, and policymakers with a thorough understanding to enhance diagnostic efficacy, ensure patient safety, and address ethical and environmental challenges, thereby informing future innovations and regulatory frameworks to promote equitable access to advanced imaging technologies globally.

Revealing Detailed Cartilage Function Through Nanoparticle Diffusion Imaging: A Computed Tomography & Finite Element Study

The ability of articular cartilage to withstand significant mechanical stresses during activities, such as walking or running, relies on its distinctive structure. Integrating detailed tissue properties into subject-specific biomechanical models is challenging due to the complexity of analyzing these characteristics. This limitation compromises the accuracy of models in replicating cartilage function and impacts predictive capabilities. To address this, methods revealing cartilage function at the constituent-specific level are essential. In this study, we demonstrated that computational modeling derived individual constituent-specific biomechanical properties could be predicted by a novel nanoparticle contrast-enhanced computer tomography (CECT) method. We imaged articular cartilage samples collected from the equine stifle joint (n = 60) using contrast-enhanced micro-computed tomography (µCECT) to determine contrast agents’ intake within the samples, and compared those to cartilage functional properties, derived from a fibril-reinforced poroelastic finite element model. Two distinct imaging techniques were investigated: conventional energy-integrating µCECT employing a cationic tantalum oxide nanoparticle (Ta2O5-cNP) contrast agent and novel photon-counting µCECT utilizing a dual-contrast agent, comprising Ta2O5-cNP and neutral iodixanol. The results demonstrate the capacity to evaluate fibrillar and non-fibrillar functionality of cartilage, along with permeability-affected fluid flow in cartilage. This finding indicates the feasibility of incorporating these specific functional properties into biomechanical computational models, holding potential for personalized approaches to cartilage diagnostics and treatment.

Bimodal MRI/Fluorescence Nanoparticle Imaging Contrast Agent Targeting Prostate Cancer.

We developed a novel site-specific bimodal MRI/fluorescence nanoparticle contrast agent targeting gastrin-releasing peptide receptors (GRPrs), which are overexpressed in aggressive prostate cancers. Biocompatible ultra-small superparamagnetic iron oxide (USPIO) nanoparticles were synthesized using glucose and casein coatings, followed by conjugation with a Cy7.5-K-8AOC-BBN [7-14] peptide conjugate. The resulting USPIO(Cy7.5)-BBN nanoparticles were purified by 100 kDa membrane dialysis and fully characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, and magnetic resonance imaging (MRI) relaxivity, as well as evaluated for in vitro and in vivo binding specificity and imaging efficacy in PC-3 prostate cancer cells and xenografted tumor-bearing mice. The USPIO(Cy7.5)-BBN nanoparticles had a core diameter of 4.93 ± 0.31 nm and a hydrodynamic diameter of 35.56 ± 0.58 nm. The r2 relaxivity was measured to be 70.2 ± 2.5 s-1 mM-1 at 7T MRI. The Cy7.5-K-8AOC-BBN [7-14] peptide-to-nanoparticle ratio was determined to be 21:1. The in vitro GRPr inhibitory binding (IC50) value was 2.5 ± 0.7 nM, indicating a very high binding affinity of USPIO(Cy7.5)-BBN to the GRPr on PC-3 cells. In vivo MRI showed significant tumor-to-muscle contrast enhancement in the uptake group at 4 h (31.1 ± 3.4%) and 24 h (25.7 ± 2.1%) post-injection compared to the blocking group (4 h: 15.3 ± 2.0% and 24 h: -2.8 ± 6.8%; p < 0.005). In vivo and ex vivo near-infrared fluorescence (NIRF) imaging revealed significantly increased fluorescence in tumors in the uptake group compared to the blocking group. These findings demonstrate the high specificity of bimodal USPIO(Cy7.5)-BBN nanoparticles towards GRPr-expressing PC-3 cells, suggesting their potential for targeted imaging in aggressive prostate cancer.

A systematic 3-D magnetic particle imaging simulation model for quantitative analysis of reconstruction image quality

Background and objectiveMagnetic particle imaging (MPI) is an emerging imaging technology in medical tomography that utilizes the nonlinear magnetization response of superparamagnetic iron oxide (SPIO) particles to determine the in vivo spatial distribution of nanoparticle contrast agents. The reconstruction image quality of MPI is determined by the characteristics of magnetic particles, the setting of the MPI scanner parameters, and the hardware interference of MPI systems. We explore a feasible method to systematically and quickly analyze the impact of these factors on MPI reconstruction image quality. MethodsWe propose a systematic 3-D MPI simulation model. The MPI simulation model has the capability of quickly producing the simulated reconstruction images of a scanned phantom, and quantitative analysis of MPI reconstruction image quality can be achieved by comparing the differences between the input image and output image. These factors are mainly classified as imaging parameters and interference parameters in our model. In order to reduce the computational time of the simulation model, we introduce GPU parallel programming to accelerate the processing of large complex matrix data. For ease of use, we also construct a reliable, high-performance, and open-source 3-D MPI simulation software tool based on our model. The efficiency of our model is evaluated by using OpenMPIData. To demonstrate the capabilities of our model, we conduct simulation experiments using parameters consistent with a real MPI scanner for improving MPI image quality. ResultsThe experimental results show that our simulation model can systematically and quickly evaluate the impact of imaging parameters and interference parameters on MPI reconstruction image quality. ConclusionsWe developed an easy-to-use and open-source 3-D MPI simulation software tool based on our simulation model incorporating all the stages of MPI formation, from signal acquisition to image reconstruction. In the future, our simulation model has potential guiding significance to practical MPI images.

Computed tomography technologies to measure key structural features of polymeric biomedical implants from bench to bedside.

Implanted polymeric devices, designed to encourage tissue regeneration, require porosity. However, characterizing porosity, which affects many functional device properties, is non-trivial. Computed tomography (CT) is a quick, versatile, and non-destructive way to gain 3D structural information, yet various CT technologies, such as benchtop, preclinical and clinical systems, all have different capabilities. As system capabilities determine the structural information that can be obtained, seamless monitoring of key device features through all stages of clinical translation must be engineered intentionally. Therefore, in this study we tested feasibility of obtaining structural information in pre-clinical systems and high-resolution micro-CT (μCT) under physiological conditions. To overcome the low CT contrast of polymers in hydrated environments, radiopaque nanoparticle contrast agent was incorporated into porous devices. The size of resolved features in porous structures is highly dependent on the resolution (voxel size) of the scan. As the voxel size of the CT scan increased (lower resolution) from 5 to 50 μm, the measured pore size was overestimated, and percentage porosity was underestimated by nearly 50%. With the homogeneous introduction of nanoparticles, changes to device structure could be quantified in the hydrated state, including at high-resolution. Biopolymers had significant structural changes post-hydration, including a mean increase of 130% in pore wall thickness that could potentially impact biological response. By incorporating imaging capabilities into polymeric devices, CT can be a facile way to monitor devices from initial design stages through to clinical translation.

Ultrasonographic Contrast and Therapeutic Effects of Hydrogen Peroxide-Responsive Nanoparticles in a Rat Model with Sciatic Neuritis.

Peripheral nerve damage lacks an appropriate diagnosis consistent with the patient's symptoms, despite expensive magnetic resonance imaging or electrodiagnostic assessments, which cause discomfort. Ultrasonography is valuable for diagnosing and treating nerve lesions; however, it is unsuitable for detecting small lesions. Poly(vanillin-oxalate) (PVO) nanoparticles are prepared from vanillin, a phytochemical with antioxidant and anti-inflammatory properties. Previously, PVO nanoparticles were cleaved by H2O2 to release vanillin, exert therapeutic efficacy, and generate CO2 to increase ultrasound contrast. However, the role of PVO nanoparticles in peripheral nerve lesion models is still unknown. Herein, we aimed to determine whether PVO nanoparticles can function as contrast and therapeutic agents for nerve lesions. To induce sciatic neuritis, rats were administered a perineural injection of carrageenan using a nerve stimulator under ultrasonographic guidance, and PVO nanoparticles were injected perineurally to evaluate ultrasonographic contrast and therapeutic effects. Reverse transcription-quantitative PCR was performed to detect mRNA levels of pro-inflammatory cytokines, ie, tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2. In the rat model of sciatic neuritis, PVO nanoparticles generated CO2 bubbles to increase ultrasonographic contrast, and a single perineural injection of PVO nanoparticles suppressed the expression of tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2, reduced the expression of F4/80, and increased the expression of GAP43. The results of the current study suggest that PVO nanoparticles could be developed as ultrasonographic contrast agents and therapeutic agents for nerve lesions.

Advances in nanoprobes for molecular MRI of Alzheimer's disease.

Alzheimer's disease is the most common cause of dementia and a leading cause of mortality in the elderly population. Diagnosis of Alzheimer's disease has traditionally relied on evaluation of clinical symptoms for cognitive impairment with a definitive diagnosis requiring post-mortem demonstration of neuropathology. However, advances in disease pathogenesis have revealed that patients exhibit Alzheimer's disease pathology several decades before the manifestation of clinical symptoms. Magnetic resonance imaging (MRI) plays an important role in the management of patients with Alzheimer's disease. The clinical availability of molecular MRI (mMRI) contrast agents can revolutionize the diagnosis of Alzheimer's disease. In this article, we review advances in nanoparticle contrast agents, also referred to as nanoprobes, for mMRI of Alzheimer's disease. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

MRI Detection of Lymph Node Metastasis through Molecular Targeting of C-C Chemokine Receptor Type 2 and Monocyte Hitchhiking.

Biopsy is the clinical standard for diagnosing lymph node (LN) metastasis, but it is invasive and poses significant risk to patient health. Magnetic resonance imaging (MRI) has been utilized as a noninvasive alternative but is limited by low sensitivity, with only ∼35% of LN metastases detected, as clinical contrast agents cannot discriminate between healthy and metastatic LNs due to nonspecific accumulation. Nanoparticles targeted to the C-C chemokine receptor 2 (CCR2), a biomarker highly expressed in metastatic LNs, have the potential to guide the delivery of contrast agents, improving the sensitivity of MRI. Additionally, cancer cells in metastatic LNs produce monocyte chemotactic protein 1 (MCP1), which binds to CCR2+ inflammatory monocytes and stimulates their migration. Thus, the molecular targeting of CCR2 may enable nanoparticle hitchhiking onto monocytes, providing an additional mechanism for metastatic LN targeting and early detection. Hence, we developed micelles incorporating gadolinium (Gd) and peptides derived from the CCR2-binding motif of MCP1 (MCP1-Gd) and evaluated the potential of MCP1-Gd to detect LN metastasis. When incubated with migrating monocytes in vitro, MCP1-Gd transport across lymphatic endothelium increased 2-fold relative to nontargeting controls. After administration into mouse models with initial LN metastasis and recurrent LN metastasis, MCP1-Gd detected metastatic LNs by increasing MRI signal by 30-50% relative to healthy LNs. Furthermore, LN targeting was dependent on monocyte hitchhiking, as monocyte depletion decreased accumulation by >70%. Herein, we present a nanoparticle contrast agent for MRI detection of LN metastasis mediated by CCR2-targeting and demonstrate the potential of monocyte hitchhiking for enhanced nanoparticle delivery.

Metabolomics-derived biomarkers for biosafety assessment of Gd-based nanoparticle magnetic resonance imaging contrast agents.

With the rapid development of nanotechnology and biomedicine, numerous gadolinium (Gd)-based nanoparticle MRI contrast agents have been widely investigated. Due to the unique physicochemical properties of nanoparticles and the complexity of biological systems, the biosafety of Gd-based nanoparticle MRI contrast agents has been paid more and more attention. Herein, for the first time, we employed an ultra-high performance liquid chromatography-electrospray ionization quadrupole time-of-flight/mass spectrometry (UPLC-ESI-QTOF/MS)-based metabolomics approach to investigate the potential toxicity of Gd-based nanoparticle MRI contrast agents. In this work, NaGdF4 and PEG-NaGdF4 nanoparticles were successfully constructed and selected as the representative Gd-based nanoparticle MRI contrast agents for the metabolomics analysis. Based on the results of metabolomics, more metabolic biomarkers and pathways were identified in the NaGdF4 group than those in the PEG-NaGdF4 group. Careful analysis of these metabolic biomarkers and pathways suggested that NaGdF4 nanoparticles induced disturbance of pyrimidine and purine metabolism, inflammatory response, and kidney injury to a certain extent compared with PEG-NaGdF4 nanoparticles. These results indicated that Gd-based nanoparticle contrast agents modified with PEG had better biosafety. Additionally, it was demonstrated that the discovery of characteristic metabolomics biomarkers induced by nanoparticles would provide a new approach for biosafety assessment and stimulate the development of nanomedicine.

Cationic tantalum oxide nanoparticle contrast agent for micro computed tomography reveals articular cartilage proteoglycan distribution and collagen architecture alterations

ObjectiveCationic tantalum oxide nanoparticles (Ta2O5-cNPs), as a newly introduced contrast agent for computed tomography (CT) of cartilage, offer quantitative evaluation of proteoglycan content and biomechanical properties. However, knowledge on the depth-wise impact of cartilage constituents on NP diffusion, particularly the influence of the collagen network, is lacking. In this study, we aim to establish the depth-dependent relationship between Ta2O5-cNP diffusion and cartilage constituents (proteoglycan content, collagen content and network architecture). MethodsOsteochondral samples (n = 30) were harvested from healthy equine stifle joints (N = 15) and the diffusion of 2.55 nm diameter cationic Ta2O5-cNPs into the cartilage was followed with µCT imaging for up to 96 hours. The diffusion-related parameters, Ta2O5-cNP maximum partition (Pmax) and diffusion time constant, were compared against biomechanical and depth-wise structural properties. Biomechanics were assessed using a stress-relaxation and sinusoidal loading protocols, whereas proteoglycan content, collagen content and collagen network architecture were determined using digital densitometry, Fourier-transform infrared spectroscopy and polarized light microscopy, respectively. ResultsThe Pmax correlates with the depth-wise distribution of proteoglycans (bulk Spearman’s ρ = 0.87, p < 0.001). More open collagen network architecture at the superficial zone enhances intake of Ta2O5-cNPs, but collagen content overall decreases the intake. The Pmax values correlate with the equilibrium modulus (ρ = 0.80, p < 0.001) of articular cartilage. ConclusionThis study establishes the feasibility of Ta2O5-cNPs for the precise and comprehensive identification of biomechanical and structural changes in articular cartilage via contrast-enhanced µCT.

CT and X-ray contrast agents: Current clinical challenges and the future of contrast.

Computed tomography (CT) is a powerful and widely used imaging technique in modern medicine. However, it often requires the use of contrast agents to visualize structures with similar radiographic density. Unfortunately, current clinical contrast agents (CAs) for CT have remained largely unchanged for decades and come with several significant drawbacks, including serious nephrotoxicity and short circulation half-lives. The next generation of CT radiocontrast agents should strive to be long-circulating, non-toxic, and non-immunogenic. Nanoparticle contrast agents have shown promise in recent years and are likely to comprise the majority of next-generation CT contrast agents. This review highlights the fundamental mechanism and background of X-ray and contrast agents. It also focuses on the challenges associated with current clinical contrast agents and provides a brief overview of potential future agents that are based on various materials such as lipids, polymers, dendrimers, metallic, and non-metallic inorganic nanoparticles (NPs). STATEMENT OF SIGNIFICANCE: We realized a need for clarification on a number of concerns related to the use of iodinated contrast material as debates regarding the safety of these agents with patients with kidney disease, shellfish allergies, and thyroid dysfunction remain ongoing in medical practice. This review was partially inspired by debates witnessed in medical practice regarding outdated misconceptions of contrast material that warrant clarification in translational and clinical arenas. Given that conversation around currently available agents is at somewhat of a high water mark, and nanoparticle research has now reached an unprecedented number of readers, we find that this review is timely and unique in the context of recent discussions in the field.

Comparison of Ultrasound Contrast between H2O2-Responsive Nanoparticles and Microbubble Contrast According to Muscle Injury in Rat Models.

Ultrasound contrast agents are clinically used for diagnosis of internal organs, but ultrasound contrast agents are rarely applied clinically in musculoskeletal disorders. Our study aims to comparatively analyze the differences between ultrasonographic images through peri-injury injection of the clinically used microbubble and researched nanoparticle contrast agents in various muscular injury models. To compare contrast-enhanced images in different muscle injury models, we prepared groups of rats with sham, laceration, punch, contusion, and toxin injection injuries. We measured H2O2 levels using the Amplex Red assay by extracting tissue from the damaged area. As comparative contrast agents, SonoVue®, a commercially available microbubble contrast agent, and poly(vanillinoxalte) (PVO) nanoparticles, which are H2O2-responsive nanoparticles, were used. The difference in contrast between the two contrast agents was recorded as an ultrasound movie, and J-image software 1.53p was used to quantify and analyze the maximum and minimum echogenicity values of the images after contrast enhancement. In the Amplex red assay for the highest H2O2 level in each muscle injury model, the maximum level showed 24 h after the modeling. In the sham rats, PVO injection showed no increased echogenicity except at the needle insertion site, but SonoVue® injection showed increased echo signal throughout the injected muscle immediately after injection. One day after the preparation of the lesion, PVO and SonoVue® were injected into the lesion site and ultrasound was performed on the lesion site. After the injection of PVO nanoparticles, contrast enhancement was observed at the lesion site immediately. SonoVue® injections, on the other hand, showed a widespread pattern of echo signals and an increase in echo retention only at the lesion site over time, but this was not clear. There were statistically significant differences between the highest and lowest echogenicity in PVO and SonoVue® contrast-enhanced images in all models. Contrast enhancement lasted more than 3 h in the PVO injection, but disappeared within 3 h in the SonoVue® injection. PVO nanoparticles showed the possibility of physiologic contrast by CO2 generated by conjugation with H2O2 generated by muscle injuries, and SonoVue® injection observed the possibility of microbubble contrast as a contrast agent with a pooling effect that lasts longer on the lesion. Further research is needed to investigate the use of various ultrasound contrast agents, including nanoparticles, in musculoskeletal disorders, as well as the potential for further utilities of microbubble contrast agents.

Nanoparticle contrast technology-based protective effects of amiodarone catheter perfusion on cardiac injury caused by radiofrequency ablation

Nanoparticle contrast technology-based protective effects of amiodarone catheter perfusion on cardiac injury caused by radiofrequency ablation

A Comparative Study of Ultrasmall Calcium Carbonate Nanoparticles for Targeting and Imaging Atherosclerotic Plaque.

Atherosclerosis is a complex disease that can lead to life-threatening events, such as myocardial infarction and ischemic stroke. Despite the severity of this disease, diagnosing plaque vulnerability remains challenging due to the lack of effective diagnostic tools. Conventional diagnostic protocols lack specificity and fail to predict the type of atherosclerotic lesion and the risk of plaque rupture. To address this issue, technologies are emerging, such as noninvasive medical imaging of atherosclerotic plaque with customized nanotechnological solutions. Modulating the biological interactions and contrast of nanoparticles in various imaging techniques, including magnetic resonance imaging, is possible through the careful design of their physicochemical properties. However, few examples of comparative studies between nanoparticles targeting different hallmarks of atherosclerosis exist to provide information about the plaque development stage. Our work demonstrates that Gd (III)-doped amorphous calcium carbonate nanoparticles are an effective tool for these comparative studies due to their high magnetic resonance contrast and physicochemical properties. In an animal model of atherosclerosis, we compare the imaging performance of three types of nanoparticles: bare amorphous calcium carbonate and those functionalized with the ligands alendronate (for microcalcification targeting) and trimannose (for inflammation targeting). Our study provides useful insights into ligand-mediated targeted imaging of atherosclerosis through a combination of in vivo imaging, ex vivo tissue analysis, and in vitro targeting experiments.

Functional attachment of primary neurons and glia on radiopaque implantable biomaterials for nerve repair

Repairing peripheral nerve injuries remains a challenge, even with use of auxiliary implantable biomaterial conduits. After implantation the location or function of polymeric devices cannot be assessed via clinical imaging modalities. Adding nanoparticle contrast agents into polymers can introduce radiopacity enabling imaging using computed tomography. Radiopacity must be balanced with changes in material properties impacting device function. In this study radiopaque composites were made from polycaprolactone and poly(lactide-co-glycolide) 50:50 and 85:15 with 0–40 wt% tantalum oxide (TaOx) nanoparticles. To achieve radiopacity, ≥5 wt% TaOx was required, with ≥20 wt% TaOx reducing mechanical properties and causing nanoscale surface roughness. Composite films facilitated nerve regeneration in an in vitro co-culture of adult glia and neurons, measured by markers for myelination. The ability of radiopaque films to support regeneration was driven by the properties of the polymer, with 5–20 wt% TaOx balancing imaging functionality with biological response and proving that in situ monitoring is feasible.

Giving Gold Wings: Ultrabright and Fragmentation Free Mass Spectrometry Reporters for Barcoding, Bioconjugation Monitoring, and Data Storage

AbstractThe widespread application of laser desorption/ionization mass spectrometry (LDI‐MS) highlights the need for a bright and multiplexable labeling platform. While ligand‐capped Au nanoparticles (AuNPs) have emerged as a promising LDI‐MS contrast agent, the predominant thiol ligands suffer from low ion yields and extensive fragmentation. In this work, we develop a N‐heterocyclic carbene (NHC) ligand platform that enhances AuNP LDI‐MS performance. NHC scaffolds are tuned to generate barcoded AuNPs which, when benchmarked against thiol‐AuNPs, are bright mass tags and form unfragmented ions in high yield. To illustrate the transformative potential of NHC ligands, the mass tags were employed in three orthogonal applications: monitoring a bioconjugation reaction, performing multiplexed imaging, and storing and reading encoded information. These results demonstrate that NHC‐nanoparticle systems are an ideal platform for LDI‐MS and greatly broaden the scope of nanoparticle contrast agents.

Giving Gold Wings: Ultrabright and Fragmentation Free Mass Spectrometry Reporters for Barcoding, Bioconjugation Monitoring, and Data Storage.

The widespread application of laser desorption/ionization mass spectrometry (LDI-MS) highlights the need for a bright and multiplexable labeling platform. While ligand-capped Au nanoparticles (AuNPs) have emerged as a promising LDI-MS contrast agent, the predominant thiol ligands suffer from low ion yields and extensive fragmentation. In this work, we develop a N-heterocyclic carbene (NHC) ligand platform that enhances AuNP LDI-MS performance. NHC scaffolds are tuned to generate barcoded AuNPs which, when benchmarked against thiol-AuNPs, are bright mass tags and form unfragmented ions in high yield. To illustrate the transformative potential of NHC ligands, the mass tags were employed in three orthogonal applications: monitoring a bioconjugation reaction, performing multiplexed imaging, and storing and reading encoded information. These results demonstrate that NHC-nanoparticle systems are an ideal platform for LDI-MS and greatly broaden the scope of nanoparticle contrast agents.