Browse
Submit Data
Databases
API
Help

Dataset Information

5 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Pilot study on biocompatibility of fluorescent nanodiamond-(NV)-Z~800 particles in rats: safety, pharmacokinetics, and bio-distribution (part III).

ABSTRACT:

Introduction

We hereby report on studies aimed to characterize safety, pharmacokinetics, and bio-distribution of fluorescent nanodiamond particles (NV)-Z~800 (FNDP-(NV)) administered to rats by intravenous infusion in a single high dose.

Methods

Broad scale biological variables were monitored following acute (90 minutes) and subacute (5 or 14 days) exposure to FNDP-(NV). Primary endpoints included morbidity and mortality, while secondary endpoints focused on hematology and clinical biochemistry biomarkers. Particle distribution (liver, spleen, lung, heart, and kidney) was assessed by whole organ near infrared imaging using an in vivo imaging system. This was validated by the quantification of particles extracted from the same organs and visualized by fluorescent and scanning electron microscopy. FNDP-(NV)-treated rats showed no change in morbidity or mortality and preserved normal motor and sensory function, as assessed by six different tests.

Results

Blood cell counts and plasma biochemistry remained normal. The particles were principally distributed in the liver and spleen. The liver particle load accounted for 51%, 24%, and 18% at 90 minutes, 5 days, and 14 days, respectively. A pilot study of particle clearance from blood indicated 50% clearance 33 minutes following the end of particle infusion.

Conclusion

We concluded that systemic exposure of rats to a single high dose of FDNP-(NV)-Z~800 (60 mg/kg) appeared to be safe and well tolerated over at least 2 weeks. These data suggest that FNDP-(NV) should proceed to preclinical development in the near future.

SUBMITTER: Barone FC

PROVIDER: S-EPMC6149985 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Long-term biocompatibility of fluorescent diamonds-(NV)-Z~800 nm in rats: survival, morbidity, histopathology, particle distribution and excretion studies (part IV).

Project description:Background:Thromboembolic events are a major cause of heart attacks and strokes. However, diagnosis of the location of high risk vascular clots is hampered by lack of proper technologies for their detection. We recently reported on bio-engineered fluorescent diamond-(NV)-Z~800nm (FNDP-(NV)) conjugated with bitistatin (Bit) and proven its ability to identify iatrogenic blood clots in the rat carotid artery in vivo by Near Infra-Red (NIR) monitored by In Vivo Imaging System (IVIS). Purpose:The objective of the present research was to assess the in vivo biocompatibility of FNDP-(NV)-Z~800nm infused intravenously to rats. Multiple biological variables were assessed along this 12 week study commissioned in anticipation of regulatory requirements for a long-term safety assessment. Methods:Rats were infused under anesthesia with aforementioned dose of the FNDP-(NV), while equal number of animals served as control (vehicle treated). Over the 12 week observation period rats were tested for thriving, motor, sensory and cognitive functions. At the termination of study, blood samples were obtained under anesthesia for comprehensive hematology and biochemical assays. Furthermore, 6 whole organs (liver, spleen, brain, heart, lung and kidney) were collected and examined ex vivo for FNDP-NV) via NIR monitored by IVIS and histochemical inspection. Results:All animals survived, thrived (no change in body and organ growth). Neuro-behavioral functions remain intact. Hematology and biochemistry (including liver and kidney functions) were normal. Preferential FNDP-(NV) distribution identified the liver as the main long-term repository. Certified pathology reports indicated no outstanding of finding in all organs. Conclusion:The present study suggests outstanding biocompatibility of FNDP-(NV)-Z~800nm after long-term exposure in the rat.

| S-EPMC6391148 | biostudies-literature

Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor ?IIb?3 and activated platelets.

Project description:Thromboembolic events (TEE) underwrite key causes of death in developed countries. While advanced imaging technologies such as computed tomography scans serve to diagnose blood clots during acute cardiovascular events, no such technology is available in routine primary care for TEE risk assessment. Here, we describe an imaging platform technology based on bioengineered fluorescent nanodiamond particles (F-NDPs) functionalized with bitistatin (Bit), a disintegrin that specifically binds to the ?IIb?3 integrin, platelet fibrinogen receptor (PFR) on activated platelets. Covalent linkage of purified Bit to F-NDP was concentration-dependent and saturable, as validated by enzyme-linked immunosorbent assay using specific anti-Bit antibodies. F-NDP-Bit interacted with purified PFR, either in immobilized or soluble form. Lotrafiban, a nonpeptide, ?IIb?3 receptor antagonist, specifically blocked F-NDP-Bit-PFR complex formation. Moreover, F-NDP-Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP). Our results suggest that engineered F-NDP-Bit particles could serve as noninvasive, "real-time" optical diagnostics for clots present in blood vessels.

| S-EPMC5440039 | biostudies-literature

The Response of HeLa Cells to Fluorescent NanoDiamond Uptake.

Project description:Fluorescent nanodiamonds are promising probes for nanoscale magnetic resonance measurements. Their physical properties predict them to have particularly useful applications in intracellular analysis. Before using them in intracellular experiments however, it should be clear whether diamond particles influence cell biology. While cytotoxicity has already been ruled out in previous studies, we consider the non-fatal influence of fluorescent nanodiamonds on the formation of reactive oxygen species (an important stress indicator and potential target for intracellular sensing) for the first time. We investigated the influence of different sizes, shapes and concentrations of nanodiamonds on the genetic and protein level involved in oxidative stress-related pathways of the HeLa cell, an important model cell line in research. The changes in viability of the cells and the difference in intracellular levels of free radicals, after diamond uptake, are surprisingly small. At lower diamond concentrations, the cellular metabolism cannot be distinguished from that of untreated cells. This research supports the claims of non-toxicity and includes less obvious non-fatal responses. Finally, we give a handhold concerning the diamond concentration and size to use for non-toxic, intracellular measurements in favour of (cancer) research in HeLa cells.

| S-EPMC5855215 | biostudies-literature

Continuous Glucose Monitoring Enabled by Fluorescent Nanodiamond Boronic Hydrogel.

Project description:Continuous monitoring of glucose allows diabetic patients to better maintain blood glucose level by altering insulin dosage or diet according to prevailing glucose values and thus to prevent potential hyperglycemia and hypoglycemia. However, current continuous glucose monitoring (CGM) relies mostly on enzyme electrodes or micro-dialysis probes, which suffer from insufficient stability, susceptibility to corrosion of electrodes, weak or inconsistent correlation, and inevitable interference. A fluorescence-based glucose sensor in the skin will likely be more stable, have improved sensitivity, and can resolve the issues of electrochemical interference from the tissue. This study develops a fluorescent nanodiamond boronic hydrogel system in porous microneedles for CGM. Fluorescent nanodiamond is one of the most photostable fluorophores with superior biocompatibility. When surface functionalized, the fluorescent nanodiamond can integrate with boronic polymer and form a hydrogel, which can produce fluorescent signals in response to environmental glucose concentration. In this proof-of-concept study, the strategy for building a miniatured device with fluorescent nanodiamond hydrogel is developed. The device demonstrates remarkable long-term photo and signal stability in vivo with both small and large animal models. This study presents a new strategy of fluorescence based CGM toward treatment and control of diabetes.

| S-EPMC9982560 | biostudies-literature

The interaction of fluorescent nanodiamond probes with cellular media.

Project description:Fluorescent nanodiamonds (FNDs) are promising tools to image cells, bioanalytes and physical quantities such as temperature, pressure, and electric or magnetic fields with nanometer resolution. To exploit their potential for intracellular applications, the FNDs have to be brought into contact with cell culture media. The interactions between the medium and the diamonds crucially influence sensitivity as well as the ability to enter cells. The authors demonstrate that certain proteins and salts spontaneously adhere to the FNDs and may cause aggregation. This is a first investigation on the fundamental questions on how (a) FNDs interact with the medium, and (b) which proteins and salts are being attracted. A differentiation between strongly binding and weakly binding proteins is made. Not all proteins participate in the formation of FND aggregates. Surprisingly, some main components in the medium seem to play no role in aggregation. Simple strategies to prevent aggregation are discussed. These include adding the proteins, which are naturally present in the cell culture to the diamonds first and then inserting them in the full medium. Graphical abstractSchematic of the interaction of nanodiamonds with cell culture medium. Certain proteins and salts adhere to the diamond surface and lead to aggregation or to formation of a protein corona.

| S-EPMC5346409 | biostudies-literature

Gd(III)-nanodiamond conjugates for MRI contrast enhancement.

Project description:A Gd(III)-nanodiamond conjugate [Gd(III)-ND] was prepared and characterized, enabling detection of nanodiamonds by MR imaging. The Gd(III)-ND particles significantly reduced the T(1) of water protons with a per-Gd(III) relaxivity of 58.82 +/- 1.18 mM(-1) s(-1) at 1.5 T (60 MHz). This represents a 10-fold increase compared to the monomer Gd(III) complex (r(1) = 5.42 +/- 0.20 mM(-1) s(-1)) and is among the highest per-Gd(III) relaxivities reported.

| S-EPMC2829273 | biostudies-literature

Generally Applicable Transformation Protocols for Fluorescent Nanodiamond Internalization into Cells.

Project description:Fluorescent nanodiamonds (FNDs) are promising nanoprobes, owing to their stable and magnetosensitive fluorescence. Therefore they can probe properties as magnetic resonances, pressure, temperature or strain. The unprecedented sensitivity of diamond defects can detect the faint magnetic resonance of a single electron or even a few nuclear spins. However, these sensitivities are only achieved if the diamond probe is close to the molecules that need to be detected. In order to utilize its full potential for biological applications, the diamond particle has to enter the cell. Some model systems, like HeLa cells, readily ingest particles. However, most cells do not show this behavior. In this article we show for the first time generally applicable methods, which are able to transport fluorescent nanodiamonds into cells with a thick cell wall. Yeast cells, in particular Saccharomyces cerevisiae, are a favored model organism to study intracellular processes including aging on a cellular level. In order to introduce FNDs in these cells, we evaluated electrical transformation and conditions of chemical permeabilization for uptake efficiency and viability. 5% DMSO (dimethyl sulfoxide) in combination with optimized chemical transformation mix leads to high uptake efficiency in combination with low impact on cell biology. We have evaluated all steps in the procedure.

| S-EPMC5517665 | biostudies-literature

Facile Amine Termination of Nanodiamond Particles and Their Surface Reaction Dynamics.

Project description:Nanodiamond synthesized by the detonation method is a composite of sp3/sp2 carbon structures; amorphous and disordered-sp2 carbons populate the surface of a sp3 diamond core lattice. Because of the production process, various elemental impurities such as N, O, H, and so forth are inherent in interstitial sites or the surface carbon (sp2/amorphous) network. Herein, the reaction dynamics on the surface of ultradisperse diamond (UDD) due to the surface transformation or reconstruction during annealing in vacuum with temperatures ranging from ambient to 800 °C is described. In situ measurement of Fourier transform infrared spectroscopic analysis shows that low-temperature (<500 °C) annealing of UDD in vacuum results in isonitrile/isocyanide (-N=C:) and nitrile functionalization (-C≡N) on the surface. At temperatures ∼500 °C, the surface hydrogenation of UDD is initiated. During annealing at 780-800 °C, the nitrile group (-C≡N) is reduced to the primary amine (NH2), and isonitrile (-N=C:) turns it to be in the saturated () structure. On exposure to air, the obtained isonitrile is transformed to an N-formyl derivative (Aryl/R-NH-CHO) structure via hydrolysis. This study provides a fundamental insight into the surface reactive profile of UDD which could lead to facile surface functionalization properties and their applications in various fields such as biomedical, biosensing, drug delivery, epoxy materials process, tribology, and possibly in cyano (-C≡N/-N=C:) chemistry.

| S-EPMC6796907 | biostudies-literature

Distributing $800 billion: an early assessment of Medicare Part D risk adjustment.

Project description:The viability and stability of the Medicare Part D prescription drug program depend on accurate risk-adjusted payments. The current approach, prescription drug hierarchical condition categories (RxHCCs), uses diagnosis and demographic information to predict future drug costs. We evaluated the performance of multiple approaches for predicting 2006 Part D drug costs and plan liability. RxHCCs explain 12 percent of the variation in actual drug costs, overpredict costs for beneficiaries with low actual costs, and underpredict costs for beneficiaries with high actual costs. Combining RxHCCs with individual-level information on prior-year drug use greatly improves performance and decreases incentives for plans to select against bad risks.

| S-EPMC2743923 | biostudies-literature

Study of Long-Term Biocompatibility and Bio-Safety of Implantable Nanogenerators.

Project description:Implantable nanogenerator (i-NG) has shown great promises for enabling self-powered implantable medical devices (IMDs). One essential requirement for practical i-NG applications is its long-term bio-compatibility and bio-safety. This paper presents a systematic study of polydimethylsiloxane (PDMS) and PDMS/Parylene-C packaged Polyvinylidene fluoride (PVDF) NGs implanted inside female ICR (Institute of Cancer Research) mice for up to six months. The PVDF NG had a stable in vitro output of 0.3 V when bended for 7200 cycles and an in vivo output of 0.1V under stretching. Multiple advanced imaging techniques, including computed tomography (CT), ultrasound, and photoacoustic were used to characterize the embedded i-NGs in vivo. The i-NGs kept excellent adhesion to the adjacent muscle surface, and exhibited stable electrical output during the entire examine period. No signs of toxicity or incompatibility were observed from the surrounding tissues, as well as from the whole body functions by pathological analyses and blood and serum test. The PDMS package was also able to effectively insulate the i-NG in biological environment with negligible stray currents at a pA scale. This series of in-vivo and in-vitro study confirmed the biological feasibility of using i-NG in vivo for biomechanical energy harvesting.

| S-EPMC6135531 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data