RESUMO
The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity5 and frequency-domain analysis6 to separate the signal from background autofluorescence7, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10-19 molar for a biotin-avidin model, 105 times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.
Assuntos
Técnicas Biossensoriais/métodos , Diagnóstico Precoce , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/genética , Nanodiamantes/química , RNA Viral/sangue , Avidina/química , Técnicas Biossensoriais/instrumentação , Biotina/química , Fluorescência , Ouro/química , HIV-1/isolamento & purificação , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Microfluídica/instrumentação , Microfluídica/métodos , Micro-Ondas , Técnicas de Amplificação de Ácido Nucleico , Papel , Plasma/virologia , Teoria Quântica , Sensibilidade e Especificidade , Imagem Individual de Molécula , TemperaturaRESUMO
Defect centers in a nanodiamond (ND) allow the detection of tiny magnetic fields in their direct surroundings, rendering them as an emerging tool for nanoscale sensing applications. Eumelanin, an abundant pigment, plays an important role in biology and material science. Here, for the first time, we evaluate the comproportionation reaction in eumelanin by detecting and quantifying semiquinone radicals through the nitrogen-vacancy color center. A thin layer of eumelanin is polymerized on the surface of nanodiamonds (NDs), and depending on the environmental conditions, such as the local pH value, near-infrared, and ultraviolet light irradiation, the radicals form and react in situ. By combining experiments and theoretical simulations, we quantify the local number and kinetics of free radicals in the eumelanin layer. Next, the ND sensor enters the cells via endosomal vesicles. We quantify the number of radicals formed within the eumelanin layer in these acidic compartments by applying optical relaxometry measurements. In the future, we believe that the ND quantum sensor could provide valuable insights into the chemistry of eumelanin, which could contribute to the understanding and treatment of eumelanin- and melanin-related diseases.
Assuntos
Melaninas , Nanodiamantes , Raios Ultravioleta , Radicais LivresRESUMO
Nanodiamonds (NDs) are considered promising delivery platforms, but inaccurate and uncontrolled release of drugs at target sites is the biggest challenge of NDs in precision medicine. This study presents the development of phototriggerable ND-based drug delivery systems, utilizing ortho-nitrobenzyl (o-NB) molecules as photocleavable linkers between drugs and nanocarriers. UV irradiation specifically cleaved o-NB molecules and then was followed by releasing antisense oligonucleotides from ND-based carriers in both buffer and cellular environments. This ND system carried cell nonpermeable therapeutic agents for bypassing lysosomal trapping and degradation. The presence of fluorescent nitrogen-vacancy centers also allowed NDs to serve as biological probes for tracing in cells. We successfully demonstrated phototriggered release of antisense oligonucleotides from ND-based nanocarriers, reactivating their antisense functions. This highlights the potential of NDs, photocleavable linkers, and light stimuli to create advanced drug delivery systems for controlled drug release in disease therapy, opening possibilities for targeted and personalized treatments.
Assuntos
Sistemas de Liberação de Medicamentos , Nanodiamantes , Oligonucleotídeos Antissenso , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/administração & dosagem , Humanos , Nanodiamantes/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Raios Ultravioleta , LuzRESUMO
Nanothermometry is increasingly demanded in frontier research in physics, chemistry, materials science and engineering, and biomedicine. An ideal thermometer should have features of reliable temperature interpretation, high sensitivity, fast response, minimum disturbance of the target's temperature, applicability in a variety of environments, and a large working temperature range. For applications in nanosystems, high spatial resolution is also desirable. Such requirements impose great challenges in nanothermometry since the shrinking of the sensor volume usually leads to a reduction in sensitivity.Diamond with nitrogen-vacancy (NV) centers provides opportunities for nanothermometry. NV center spins have sharp resonances due to their superb coherence. NV centers are multimodal sensors. They can directly sense magnetic fields, electric fields, temperature, pressure, and nuclear spins and, through proper transduction, measure other quantities such as the pH and deformation. In particular, their spin resonance frequencies vary with temperature, making them a promising thermometer. The high thermal conductivity, high hardness, chemical stability, and biocompatibility of diamond enable reliable and fast temperature sensing in complex environments ranging from erosive liquids to live systems. Chemical processing of diamond surfaces allows various functionalities such as targeting. The small size and the targeting capability of nanodiamonds then enable site-specific temperature sensing with nanoscale spatial resolution. However, the sensitivity of NV-based nanothermometry is yet to meet the requirement of practical systems with a large gap of a few orders of magnitude. On the other hand, although NV-based quantum sensing works well from 0.3 to 600 K, extending the sensing scheme to high temperature remains challenging due to uncertainty in identifying the exact physical limits and possible solution at elevated temperatures.This Account focuses on our efforts to enhance the temperature sensitivity and widen the working temperature range of diamond-based nanothermometry. We start with explaining the working principle and features of NV-based thermometry with examples of applications. Then a transducer-based concept is introduced with practical schemes to improve the sensitivity of the nanodiamond thermometer. Specifically, we show that the temperature signal can be transduced and amplified by adopting hybrid structures of nanodiamond and magnetic nanoparticles, which results in a record temperature sensitivity of 76 µK/âHz. We also demonstrate quantum sensing with NV at high temperatures of up to 1000 K by adopting a pulsed heating-cooling scheme to carry out the spin polarization and readout at room temperature and the spin manipulation (sensing) at high temperatures. Finally, unsolved problems and future endeavors of diamond nanothermometry are discussed.
Assuntos
Diamante , Nanodiamantes , Nanodiamantes/química , Temperatura , Nitrogênio/químicaRESUMO
This study describes the development of a highly sensitive amperometric biosensor for the analysis of phenolic compounds such as catechol. The biosensor architecture is based on the immobilization of tyrosinase (Tyr) on a screen-printed carbon electrode (SPE) modified with nanodiamond particles (ND), 1-butyl-3-methylimidazolium hexafluorophosphate (IL) and poly-l-lysine (PLL). Surface morphologies of the electrodes during the modification process were evaluated by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to investigate the electrochemical characteristics of the modified electrodes. Owing to the synergistic effect of the modification materials, the Tyr/PLL/ND-IL/SPE exhibited high sensitivity (328.2 µA mM-1) towards catechol with a wide linear range (5.0 × 10-8 - 1.2 × 10-5 M) and low detection limit (1.1 × 10-8 M). Furthermore, the method demonstrated good reproducibility and stability. The amperometric response of the biosensor towards other phenolic compounds such as bisphenol A, phenol, p-nitrophenol, m-cresol, p-cresol and o-cresol was also investigated. The analytical applicability of the biosensor was tested by the analysis of catechol in tap water. The results of the tap water analysis showed that the Tyr/PLL/ND-IL/SPE can be used as a practical and effective method for catechol determination.
Assuntos
Técnicas Biossensoriais , Líquidos Iônicos , Nanodiamantes , Líquidos Iônicos/análise , Polilisina , Reprodutibilidade dos Testes , Fenóis/análise , Catecóis/análise , Catecóis/química , Monofenol Mono-Oxigenase/química , Carbono/química , Água , Técnicas Biossensoriais/métodos , Eletrodos , Técnicas Eletroquímicas/métodosRESUMO
Nanometer-sized diamonds (NDs) containing nitrogen vacancy centers have garnered significant attention as potential quantum sensors for reading various types of physicochemical information in vitro and in vivo. However, NDs intrinsically aggregate when placed in biological environments, hampering their sensing capacities. To address this issue, the grafting of hydrophilic polymers onto the surface of NDs has been demonstrated considering their excellent ability to prevent protein adsorption. To this end, crowding of the grafted chains plays a crucial role because it is directly associated with the antiadsorption effect of proteins; however, its quantitative evaluation has not been reported previously. In this study, we graft poly(ethylene glycol) (PEG) with various molecular weights onto NDs, determine their crowding using a gas adsorption technique, and disclose the cross-correlation between the pH in the grafting reaction, crowding density, molecular weight, and the prevention effect on protein adsorption. PEG-grafted NDs exhibit a pronounced effect on the prevention of lung accumulation after intravenous injection in mice. PEG crowding was compared to that calculated by using a diameter determined by dynamic light scattering (DLS) assuming a sphere.
Assuntos
Técnicas Biossensoriais , Pulmão , Nanodiamantes , Polietilenoglicóis , Polietilenoglicóis/química , Adsorção , Animais , Nanodiamantes/química , Camundongos , Técnicas Biossensoriais/métodos , Proteínas/químicaRESUMO
Nanodiamonds (NDs) have garnered attention in the field of nanomedicine due to their unique properties. This review offers a comprehensive overview of NDs synthesis methods, properties, and their uses in biomedical applications. Various synthesis techniques, such as detonation, high-pressure, high-temperature, and chemical vapor deposition, offer distinct advantages in tailoring NDs' size, shape, and surface properties. Surface modification methods further enhance NDs' biocompatibility and enable the attachment of bioactive molecules, expanding their applicability in biological systems. NDs serve as promising nanocarriers for drug delivery, showcasing biocompatibility and the ability to encapsulate therapeutic agents for targeted delivery. Additionally, NDs demonstrate potential in cancer treatment through hyperthermic therapy and vaccine enhancement for improved immune responses. Functionalization of NDs facilitates their utilization in biosensors for sensitive biomolecule detection, aiding in precise diagnostics and rapid detection of infectious diseases. This review underscores the multifaceted role of NDs in advancing biomedical applications. By synthesizing NDs through various methods and modifying their surfaces, researchers can tailor their properties for specific biomedical needs. The ability of NDs to serve as efficient drug delivery vehicles holds promise for targeted therapy, while their applications in hyperthermic therapy and vaccine enhancement offer innovative approaches to cancer treatment and immunization. Furthermore, the integration of NDs into biosensors enhances diagnostic capabilities, enabling rapid and sensitive detection of biomolecules and infectious diseases. Overall, the diverse functionalities of NDs underscore their potential as valuable tools in nanomedicine, paving the way for advancements in healthcare and biotechnology.
Assuntos
Doenças Transmissíveis , Nanodiamantes , Vacinas , Humanos , Nanodiamantes/química , Sistemas de Liberação de Medicamentos , Propriedades de SuperfícieRESUMO
Peracetic acid (PAA) oxidation catalyzed by metal-free carbons is promising for advanced water decontamination. Nevertheless, developing reaction-oriented and high-performance carbocatalysts has been limited by the ambiguous understanding of the intrinsic relationship between carbon chemical/molecular structure and PAA transformation behavior. Herein, we comprehensively investigated the PAA activation using a family of well-defined sp2/sp3 carbon hybrids from annealed nanodiamonds (ANDs). The activity of ANDs displays a volcano-type trend, with respect to the sp2/sp3 ratio. Intriguingly, sp3-C-enriched AND exhibits the best catalytic activity for PAA activation and phenolic oxidation, which is different from persulfate chemistry in which the sp2 network normally outperforms sp3 hybridization. At the electron-rich sp2-C site, PAA undergoes a reduction reaction to generate a reactive complex (AND-PAA*) and induces an electron-transfer oxidation pathway. At the sp3-C site adjacent to CâO, PAA is oxidized to surface-confined OH* and O* successively, which ultimately evolves into singlet oxygen (1O2) as the primary reactive species. Benefiting from the dual nonradical regimes on sp2/sp3 hybrids, AND mediates a sustainable redox recycle with PAA to continuously generate reactive species to attack water contaminants, meanwhile maintaining structural/chemical integrity and exceptional reusability in cyclic runs.
Assuntos
Ácido Peracético , Ácido Peracético/química , Catálise , Nanodiamantes/química , Purificação da Água/métodos , Oxirredução , Poluentes Químicos da Água/química , Água/químicaRESUMO
Propranolol is currently considered as an emerging contaminant in water bodies. In this study, R- and S-propranolol were determined in river samples by electrokinetic chromatography (EKC) using nanodiamonds (NDs) and human serum albumin (HSA) as a pseudo-stationary phase in order to achieve enantioseparation. Previously, river samples were preconcentrated using a column filled with Amberlite® IR-120 and Dowex® 50WX8 resins. The setting up of influential factors such as temperature, voltage, pH, and HSA and NDs concentration is accurately described along this manuscript. A multivariate study and optimization was carried out to obtain the enantioseparation of propranolol (Rs = 2.91), which was reached under the following experimental conditions: voltage of 16 kV, temperature of 16°C, phosphate buffer pH 9.5, NDs of 0.20%, and HSA of 15 µmol l-1 . The recoveries of analytes under optimal conditions were higher than 98%. The limits of detection were 0.85 µg l-1 for R- and S-propranolol. The method was applied to real samples, and the obtained results in three different water sources studied were 1.02, 0.59, and 0.30 µg l-1 for the R-enantiomer and 0.99, 0.54, and 0.28 µg l-1 for the S-enantiomer. The accuracy of the proposed methodology (including bias and precision) has allowed us to propose it as a successful tool for the control of water quality.
Assuntos
Cromatografia Capilar Eletrocinética Micelar , Nanodiamantes , Humanos , Propranolol , Albumina Sérica Humana , Rios , Estereoisomerismo , Cromatografia Capilar Eletrocinética Micelar/métodosRESUMO
Sirtuins, often called "longevity enzymes", are pivotal in genome protection and DNA repair processes, offering insights into aging and longevity. This study delves into the potential impact of resveratrol (RV) and nanodiamonds (NDs) on sirtuin activity, focusing on two strains of house crickets (Acheta domesticus): the wild-type and long-lived strains. The general sirtuin activity was measured using colorimetric assays, while fluorescence assays assessed SIRT1 activity. Additionally, a DNA damage test and a Kaplan-Meier survival analysis were carried out. Experimental groups were fed diets containing either NDs or RV. Notably, the long-lived strain exhibited significantly higher sirtuin activity compared to the wild-type strain. Interestingly, this heightened sirtuin activity persisted even after exposure to RVs and NDs. These findings indicate that RV and NDs can potentially enhance sirtuin activity in house crickets, with a notable impact on the long-lived strain. This research sheds light on the intriguing potential of RV and NDs as sirtuin activators in house crickets. It might be a milestone for future investigations into sirtuin activity and its potential implications for longevity within the same species, laying the groundwork for broader applications in aging and lifespan extension research.
Assuntos
Nanodiamantes , Sirtuínas , Resveratrol/farmacologia , Longevidade , Sirtuína 1/genéticaRESUMO
Coatings with xenogenic materials, made of detonation nanodiamonds, provide additional strength and increase elasticity. A functionally developed surface of nanodiamonds makes it possible to apply antibiotics. Previous experiments show the stability of such coatings; however, studies on stability in the bloodstream and calcification of the material in natural conditions have yet to be conducted. Tritium-labeled nanodiamonds (negative and positive) were obtained by the tritium activation method and used to develop coatings for a pork aorta to analyze their stability in a pig's bloodstream using a radiotracer technique. A chitosan layer was applied from a solution of carbonic acid under high-pressure conditions to prevent calcification. The obtained materials were used to prepare a porcine conduit, which was surgically stitched inside the pig's aorta for four months. The aorta samples, including nanodiamond-coated and control samples, were analyzed for nanodiamond content and calcium, using the radiotracer and ICP-AES methods. A histological analysis of the materials was also performed. The obtained coatings illustrate a high in vivo stability and low levels of calcification for all types of nanodiamonds. Even though we did not use additional antibiotics in this case, the development of infection was not observed for negatively charged nanodiamonds, opening up prospects for their use in developing coatings.
Assuntos
Materiais Revestidos Biocompatíveis , Nanodiamantes , Trítio , Animais , Nanodiamantes/química , Suínos , Materiais Revestidos Biocompatíveis/química , Trítio/química , Aorta , Bioprótese , Quitosana/química , Próteses Valvulares CardíacasRESUMO
Polymer nanoparticles are widely used in drug delivery and are also a potential concern due to the increased burden of nano- or microplastics in the environment. In order to use polymer nanoparticles safely and understand their mechanism of action, it is useful to know where within cells and tissues they end up. To this end, we labeled polymer nanoparticles with nanodiamond particles. More specifically, we have embedded nanodiamond particles in the polymer particles and characterized the composites. Compared to conventional fluorescent dyes, these labels have the advantage that nanodiamonds do not bleach or blink, thus allowing long-term imaging and tracking of polymer particles. We have demonstrated this principle both in cells and entire liver tissues.
Assuntos
Nanodiamantes , Plásticos , Corantes Fluorescentes , Sistemas de Liberação de Medicamentos , PolímerosRESUMO
Nanodiamonds (NDs) are carbon nanoparticles with a large refractive index, a high density, and exceptional chemical stability. When excited by green light, they can emit bright red fluorescence from implanted nitrogen-vacancy (NV) centers. Taking advantage of these properties, we have developed antibody-conjugated NDs as in vitro diagnostic sensors for two complementary assays: particle-enhanced turbidimetric immunoassay (PETIA) and spin-enhanced lateral flow immunoassay (SELFIA). To achieve this goal, monocrystalline diamond powders (â¼100 nm in diameter) with or without NV implantation were first treated in molten KNO3 to reduce their size and shape inhomogeneity, followed by surface carboxylation in strong oxidative acids and non-covalent conjugation with antibodies in water. PETIA and SELFIA were carried out separately with a microplate reader and a magnetically modulated fluorescence analyzer. Using C-reactive protein (CRP) as the target antigen, we found that anti-CRP-conjugated NDs exhibited high colloidal stability over 1 month at 4 °C in buffer solution. The limits of detection for 3 µL of CRP sample solution were 0.06 µg/mL and 1 ng/mL with variation coefficients of less than 10 and 15% for PETIA and SELFIA, respectively. These two methods together provide a detection range of 1 ng/mL-10 µg/mL, potentially useful for clinical applications. This work represents the first practical use of rounded monocrystalline NDs as in vitro diagnostic reagents.
Assuntos
Técnicas Biossensoriais , Imunoconjugados , Nanodiamantes , Nanodiamantes/química , Imunoensaio , Diamante , Nitrogênio/química , AnticorposRESUMO
Fluorescent nanodiamonds (FNDs) with negative nitrogen-vacancy (NV- ) defect centers are great probes for biosensing applications, with potential to act as biomarkers for cell differentiation. To explore this concept, uptake of FNDs (≈120 nm) by THP-1 monocytes and monocyte-derived M0-macrophages is studied. The time course analysis of FND uptake by monocytes confirms differing FND-cell interactions and a positive time-dependence. No effect on cell viability, proliferation, and differentiation potential into macrophages is observed, while cells saturated with FNDs, unload the FNDs completely by 25 cell divisions and subsequently take up a second dose effectively. FND uptake variations by THP-1 cells at early exposure-times indicate differing phagocytic capability. The cell fraction that exhibits relatively enhanced FND uptake is associated to a macrophage phenotype which derives from spontaneous monocyte differentiation. In accordance, chemical-differentiation of the THP-1 cells into M0-macrophages triggers increased and homogeneous FND uptake, depleting the fraction of cells that were non-responsive to FNDs. These observations imply that FND uptake allows for distinction between the two cell subtypes based on phagocytic capacity. Overall, FNDs demonstrate effective cell labeling of monocytes and macrophages, and are promising candidates for sensing biological processes that involve cell differentiation.
Assuntos
Técnicas Biossensoriais , Corantes Fluorescentes , Macrófagos , Monócitos , Nanodiamantes , Fagocitose , Nanodiamantes/química , Nanodiamantes/toxicidade , Nitrogênio/química , Corantes Fluorescentes/química , Corantes Fluorescentes/toxicidade , Humanos , Linhagem Celular , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/fisiologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Fagocitose/efeitos dos fármacosRESUMO
Interest in nanodiamond (ND) has been spurred by its unique properties such as high biocompatibility, versatile surface chemistry, and the possibility to apply it as drug delivery agent, cross-linker, or coating and for sensing applications when luminescent lattice defects such as the NV centers are present in the crystal lattice. Currently, nanodiamond has been used for targeted drug delivery, phototherapeutic applications, and sensing and imaging in cellular environments and in vitro. Furthermore, suitably functionalized nanodiamond is a promising material for tissue engineering applications. However, the application of nanodiamond has long been hampered by a number of obstacles and challenges met with commercially available nanodiamonds of different origins. A major issue is related to the strong agglomeration of the individual particles resulting in covalently linked aggregates with larger sizes and a broad size distribution. Furthermore, the surface termination of typical nanodiamond particles tends to be rather inhomogeneous, containing a multitude of different functional groups. The retention of functionality of immobilized moieties for bioapplications is often not known. And finally, the surface of nanodiamond possesses a strong propensity for nonspecific interaction, especially proteins from serum, cell fluids, or the culture media used for the incubation of cells with nanodiamond. The resulting protein corona influences the possibility to access functional moieties on the diamond surface and leads to a reduced reproducibility of observations in physiological environments and a limited attribution of effects to the presence of the functional moieties on the diamond surface. In this Account, we describe our efforts to address these challenges using multiple strategies mainly for the example of detonation nanodiamond (DND). First, a homogeneous size distribution of the nanoparticles and an initial surface termination with a unique type of atoms or groups can be achieved using mechanochemical methods and treatments with different reagents in both solution and gas phases. Reactions in liquid media typically lead to more uniform results as the entire surface of the particles becomes equally accessible. We have then worked on the development of different covalent linker strategies to accommodate the grafting needs of different functional moieties and thus to enable the production of orthogonally functionalized ND particles, which can be modified with multiple moieties in a controlled fashion. The noncovalent immobilization of functional units is equally useful as it permits the conservation of functionality for sensitive proteins, which denature upon covalent immobilization. In summary, our work aims to gain full control over the surface properties of diamond nanoparticles and to develop a toolbox of chemical methods to provide functionalized and tailored nanodiamond for a plethora of biomedical applications. Further research in the field of diamond functionalization will cover also the transfer of already existing methods to other types of diamond surfaces, the production of stoichiometrically functionalized particles, the covalent and dynamic self-assembly of nanodiamond particles, and the continuing development of suitable characterization techniques.
Assuntos
Nanodiamantes , Nanodiamantes/química , Reprodutibilidade dos Testes , Propriedades de Superfície , LuminescênciaRESUMO
Relaxometry is a technique which makes use of a specific crystal lattice defect in diamond, the so-called NV center. This defect consists of a nitrogen atom, which replaces a carbon atom in the diamond lattice, and an adjacent vacancy. NV centers allow converting magnetic noise into optical signals, which dramatically increases the sensitivity of the readout, allowing for nanoscale resolution. Analogously to T1 measurements in conventional magnetic resonance imaging (MRI), relaxometry allows the detection of different concentrations of paramagnetic species. However, since relaxometry allows very local measurements, the detected signals are from nanoscale voxels around the NV centers. As a result, it is possible to achieve subcellular resolutions and organelle specific measurements.A relaxometry experiment starts with polarizing the spins of NV centers in the diamond lattice, using a strong laser pulse. Afterward the laser is switched off and the NV centers are allowed to stochastically decay into the equilibrium mix of different magnetic states. The polarized configuration exhibits stronger fluorescence than the equilibrium state, allowing one to optically monitor this transition and determine its rate. This process happens faster at higher levels of magnetic noise. Alternatively, it is possible to conduct T1 relaxation measurements from the dark to the bright equilibrium by applying a microwave pulse which brings NV centers into the -1 state instead of the 0 state. One can record a spectrum of T1 at varying strengths of the applied magnetic field. This technique is called cross-relaxometry. Apart from detecting magnetic signals, responsive coatings can be applied which render T1 sensitive to other parameters as pH, temperature, or electric field. Depending on the application there are three different ways to conduct relaxometry experiments: relaxometry in moving or stationary nanodiamonds, scanning magnetometry, and relaxometry in a stationary bulk diamond with a stationary sample on top.In this Account, we present examples for various relaxometry modes as well as their advantages and limitations. Due to the simplicity and low cost of the approach, relaxometry has been implemented in many different instruments and for a wide range of applications. Herein we review the progress that has been achieved in physics, chemistry, and biology. Many articles in this field have a proof-of-principle character, and the full potential of the technology still waits to be unfolded. With this Account, we would like to stimulate discourse on the future of relaxometry.
Assuntos
Diamante , Nanodiamantes , Diamante/química , Nitrogênio/química , Nanodiamantes/química , Fluorescência , TemperaturaRESUMO
Boron neutron capture therapy (BNCT), advanced cancer treatment utilizing nuclear fission of 10 B atom in cancer cells, is attracting increasing attention. As 10 B delivery agent, sodium borocaptate (10 BSH, 10 B12 H11 SH â 2Na), has been used in clinical studies along with L-boronophenylalanine. Recently, this boron cluster has been conjugated with lipids, polymers or nanoparticles to increase selectivity to and retentivity in tumor. In this work, anticancer nanoformulations for BNCT are designed, consisting of poly(glycerol) functionalized detonation nanodiamonds (DND-PG) as a hydrophilic nanocarrier, the boron cluster moiety (10 B12 H11 2- ) as a dense boron-10 source, and phenylboronic acid or RGD peptide as an active targeting moiety. Some hydroxy groups in PG were oxidized to carboxy groups (DND-PG-COOH) to conjugate the active targeting moiety. Some hydroxy groups in DND-PG-COOH were then transformed to azide to conjugate 10 B12 H11 2- through click chemistry. The nanodrugs were evaluated inâ vitro using B16 murine melanoma cells in terms of cell viability, BNCT efficacy and cellular uptake. As a result, the 10 B12 H11 2- moiety is found to facilitate cellular uptake probably due to its negative charge. Upon thermal neutron irradiation, the nanodrugs with 10 B12 H11 2- moiety exhibited good anticancer efficacies with slight differences with and without targeting moiety.
Assuntos
Terapia por Captura de Nêutron de Boro , Nanodiamantes , Neoplasias , Camundongos , Animais , Boro , Glicerol , Compostos de BoroRESUMO
Nanodiamonds (NDs) have attracted considerable attention owing to their quantum properties and versatility in biological applications. In this study, we systematically investigated the adsorption of DNA oligonucleotides onto NDs with three types of surface groups: carboxylated (COOH-), hydroxylated (OH-), and hydrogenated (H-). Among them, only the H-NDs showed fluorescence quenching property that is useful for real-time DNA adsorption kinetic studies. The effect of common metal ions on DNA adsorption was studied. In the presence of Na+, the order of DNA adsorption efficiency was H- > OH- > COOH-, whereas all the NDs showed a similar DNA adsorption efficiency in the presence of divalent metal ions such as Ca2+ and Zn2+. Desorption studies revealed that hydrogen bonding and metal-mediated interactions were dominant for the adsorption of DNA, and the H-NDs exhibited extraordinarily tight DNA adsorption. Finally, a fluorescently labeled DNA was adsorbed on NDs for DNA detection, and the COOH-NDs had the highest target specificity, and a detection limit of 1.4 nM was achieved. This study indicates the feasibility of using metal ions to mediate the physical adsorption of DNA to NDs and compares various NDs with graphene oxide for fundamental understanding.
Assuntos
Nanodiamantes , Adsorção , Cinética , DNARESUMO
Oil-in-water emulsions, stabilised with conventional surfactants, are commonly used in eye drops for ocular drug delivery. However, the presence of surfactants can sometimes irritate tissues. Furthermore, conventional emulsions often have poor retention on ocular tissue. Pickering emulsions stabilised with nanoparticles have been gaining attention in recent years for a range of biomedical applications because of their biocompatibility. Here, Pickering emulsions were evaluated for the first time for the confinement of organic components for potential application in ocular drug delivery. For a model system, we used nanodiamond (ND) nanoparticles functionalised with covalently-bonded two-tail (2T) oligoglycine C10(NGly4)2 to make Pickering oil-in-water emulsions, which were stable over three months of storage under neutral pH. We proved the non-toxicity of ND-2T Pickering emulsions, comparable to buffer solution, via an ex vivo bovine corneal permeability and opacity test. The retention of the oil phase in the ND-2T stabilised emulsions on corneal tissue is significantly increased because of the mucoadhesive properties arising from the positively-charged terminal amino groups of 2T. Our formulated emulsions have a surface tension, pH and salt concentration comparable to that of tear fluid. The high retention of the ND-2T-stabilised emulsions on the corneal surface, in combination with their non-toxicity, gives them distinct advantages for ocular drug delivery. The principles of this model system could be applied in the future design of a range of formulations for drug delivery.
Assuntos
Nanodiamantes , Nanopartículas , Animais , Bovinos , Emulsões/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Tensoativos , Água/química , Tamanho da PartículaRESUMO
Tofacitinib (TOF) is gaining recognition as a potent therapeutic agent for a variety of autoimmune disorders, including rheumatoid arthritis and psoriasis. Ensuring precise drug concentration control during treatment necessitates a rapid and sensitive detection method. This study introduces a novel electrochemical sensor employing a composite of nanodiamond (ND), copper aluminate spinel oxide (CuAl2O4), and iron (II, III) oxide (Fe3O4) as modified materials for efficient TOF detection. Extensive analyses using physicochemical and electrochemical techniques were carried out to characterize the morphological, structural, and electrochemical properties of the ND@CuAl2O4@Fe3O4 composite. Thereafter, various voltammetric methods were utilized to evaluate the electrochemical behavior of the ND@CuAl2O4@Fe3O4-modified glassy carbon electrode (GCE) concerning TOF determination. The fabricated electrode showcased superior performance in electrochemical TOF detection in a buffered solution (pH = 5), achieving a remarkably low detection limit of 7.8 nM and a linear response from 0.05 µM to 13.21 µM. Furthermore, applying the modified electrode as an electrochemical sensor exhibited exceptional selectivity, stability, and practicality in determining TOF in pharmaceutical and biological samples. Alongside the sensor development, this study conducted a thorough investigation using Density Functional Theory (DFT) for the geometry optimization of TOF and the TOF-ND complex. Consequently performed molecular docking studies using Janus Kinase 1 (JAK1) (PDB ID: 3EYG) and JAK3 (PDB ID: 3LXK) indicated higher interaction of the TOF-ND conjugate with the JAKs, reflected by binding energies of -12.9 kcal/mol and -11.7 kcal/mol for JAK1 and JAK3 respectively, compared to -7.0 kcal/mol and -6.9 kcal/mol for TOF alone. These findings illustrate the potential of the ND-based ND@CuAl2O4@Fe3O4 composite as a proficient sensing material for TOF detection and the merits of DFT in providing a detailed understanding of the interactions at play. This pioneering research holds promise for real-time TOF monitoring, which will advance personalized treatment strategies and improve therapeutic outcomes for patients with autoimmune disorders.