Fe-doped nanodiamond-based photo-Fenton catalyst for dual-modal fluorescence imaging and improved chemotherapeutic efficacy against tumor hypoxia.

The deficiency of oxygen in most solid tumors plays a profound role in their proliferation, metastasis, and invasion and contributes to their resistance to treatments such as radiation, chemotherapy, and photodynamic therapy (PDT). A therapeutic approach based on the Fenton reaction has received considerable interest as a means of treating cancer with ROS-based nano catalytic medicine, referred to as chemodynamic therapy (CDT). A range of modified treatment strategies are being explored to enhance both CDT and conventional methods of therapy. These include Fenton-like reactions, photo-enhanced Fenton reactions, and Fenton catalytic-enhanced synergistic therapies. In this article, we propose and demonstrate a photochemotherapy (PCT) strategy for cancer treatment utilizing near-infrared (NIR)-induced Fenton reactions using Fe-doped nanodiamond (FeND). When FeND is exposed to human lung cancer cells A549, it exhibits outstanding biocompatibility. However, when particle-treated cells are exposed to NIR laser radiation, the particle exhibits cytotoxicity to a certain degree. The anticancer medication doxorubicin (DOX) was adsorbed onto the FeND to address this issue. The conjugated DOX could undergo a redox cycle to generate excess H2O2 inside the cells, and in addition, DOX can also cause tumor cell apoptosis. Combining chemotherapy (via DOX) with a Fenton reaction results in enhanced therapeutic effectiveness. Moreover, the intrinsic fluorescence of the nanodiamond in FeND can be used to monitor the interaction of particles with cells as well as their localization, thus making it an excellent imaging probe. In our study, we found that FeND could serve as a CDT agent, biomarker, drug carrier, and potentially valuable candidate for CDT agents and contribute to the further development of more effective CDT platforms using nanodiamond.

Berberine mediated fluorescent gold nanoclusters in biomimetic erythrocyte ghosts as a nanocarrier for enhanced photodynamic treatment.

Photodynamic therapy (PDT) is a well-established cancer treatment method that employs light to generate reactive oxygen species (ROS) causing oxidative damage to cancer cells. Nevertheless, PDT encounters challenges due to its oxygen-dependent nature, which makes it less effective in hypoxic tumor environments. To address this issue, we have developed a novel nanocomposite known as AuNC@BBR@Ghost. This nanocomposite combines the advantageous features of erythrocyte ghost membranes, the photoresponsive properties of gold nanoclusters (AuNC) and the anticancer characteristics of Berberine (BBR) for cancer treatment. Our synthesized AuNC efficiently produce ROS, with a 25% increase in efficiency when exposed to near-infrared (NIR) irradiation. By harnessing the oxygen-carrying capacity of erythrocyte ghost cells, AuNC@BBR@Ghost demonstrates a significant improvement in ROS generation, achieving an 80% efficiency. Furthermore, the AuNC exhibit tunable emission wavelengths due to their excellent fluorescent properties. In normoxic conditions, treatment of A549 lung carcinoma cells with AuNC@BBR@Ghost followed by exposure to 808 nm NIR irradiation results in a notable increase in intracellular ROS levels, accelerating cell death. In hypoxic conditions, when A549 cells were treated with AuNC@BBR@Ghost, the erythrocyte ghost acted as an oxygen supplement due to the residual hemoglobin, alleviating hypoxia and enhancing the nanocomposite's sensitivity to PDT treatment. Thus, the AuNC@BBR@Ghost nanocomposite achieves an improved effect by combining the advantageous properties of its individual components, resulting in enhanced ROS generation and adaptability to hypoxic conditions. This innovative approach successfully overcomes PDT's limitations, making AuNC@BBR@Ghost a promising nanotheranostic agent with significant potential for advanced cancer therapy.

Precise Sn-Doping Modulation for Optimizing CdWO4 Nanorod Photoluminescence.

The cadmium tungstate rods have been given much attention due to their potential for usage in numerous luminescent applications. We have prepared single crystalline Sn-doped Cd1-xSnxWO4 (where x = 0, 1, 3, and 5%) nanorods (NRDs) and characterized them using refined X-ray diffraction and TEM analysis, revealing a monoclinic phase and a crystallite size that decreased from 62 to 38 nm as Sn concentration increased. Precise Sn doping modulation in CdWO4 NRDs causes surface recombination of electrons and holes, which causes the PL intensity to decrease as the Sn content rises. The chromaticity diagram shows that an increase in the Sn content caused a change in the emission color from sky blue to light green, which was attributed to the increased defect density. The photoluminescence time decay curve of all samples fit well with double-order exponential decay, and the average decay lifetime was found to be 1.11, 0.93, and 1.16 ns for Cd1-xSnxWO4, x = 0, 1, and 5%, respectively. This work provides an understanding of the behavior of Sn-doped CdWO4 NRDs during electron transitions and the physical nature of emission that could be used in bio-imaging, light sources, displays, and other applications.

Nanodiamond-Induced Thrombocytopenia in Mice Involve P-Selectin-Dependent Nlrp3 Inflammasome-Mediated Platelet Aggregation, Pyroptosis and Apoptosis.

Nanodiamond (ND) has been developed as a carrier to conduct various in vivo diagnostic and therapeutic uses. Safety is one of the major considerations, while the hemocompatibility of ND is not clearly addressed. Here we found that, compared to the other sizes of ND with relatively inert properties, treatments of 50 nm ND induced stronger platelet aggregation, platelet pyroptosis, apoptosis and thrombocytopenia in mice. Blockage treatments of soluble P-selectin, reactive oxygen species (ROS), and Nlrp3 inflammasome inhibitors markedly suppressed such adverse effects, suggesting ND-induced platelet activation and pyroptosis involves surface P-selectin-mediated enhancement of mitochondrial superoxide levels and Nlrp3 inflammasome activation. In addition, challenges of NDs induced less platelet pyroptosis and displayed less thrombocytopenia in P-selectin (Selp-/- ), Nlrp3 (Nlrp3-/- ) and caspase-1 (Casp1-/- ) mutants, as compared to the wild type mice. Blockers of P-selectin, ROS, and Nlrp3 inflammasome pathways could be considered as antidotes for ND induced platelet activation and thrombocytopenia.

Multimodal bioimaging using nanodiamond and gold hybrid nanoparticles.

Hybrid core-shell nanodiamond-gold nanoparticles were synthesized and characterized as a novel multifunctional material with tunable and tailored properties for multifunctional biomedical applications. The combination of nanostructured gold and nanodiamond properties afford new options for optical labeling, imaging, sensing, and drug delivery, as well as targeted treatment. ND@Au core-shell nanoparticles composed of nanodiamond (ND) core doped with Si vacancies (SiV) and Au shell were synthesized and characterized in terms of their biomedical applications. Several bioimaging modalities based on the combination of optical and spectroscopic properties of the hybrid nano-systems are demonstrated in cellular and developing zebrafish larvae models. The ND@Au nanoparticles exhibit isolated ND's Raman signal of sp3 bonded carbon, one-photon fluorescence of SiV with strong zero-phonon line at 740 nm, two-photon excited fluorescence of nanogold with short fluorescence lifetime and strong absorption of X-ray irradiation render them possible imaging agent for Raman mapping, Fluorescence imaging, two-photon Fluorescence Lifetime Imaging (TP-FLIM) and high-resolution hard-X-ray microscopy in biosystems. Potential combination of the imaging facilities with other theranostic functionalities is discussed.

Multifunctional plasmonic gold nanostars for cancer diagnostic and therapeutic applications.

Gold nanostar (AuNSt) has gained great attention in bioimaging and cancer therapy due to their tunable surface plasmon resonance across the visible-near infrared range. Photothermal treatment and imaging capabilities including fluorescence lifetime imaging at two-photon excitation (TP-FLIM) and dark-field microscopic imaging are considered in this work. Two types of AuNSts having plasmon absorption peaks centred at 600 and 750 nm wavelength were synthesized and studied. Both NSts exhibited low cytotoxicity on A549 human lung carcinoma cells. A strong emission at two-photon excitation was observed for both NSts, well-distinguishable from lifetimes of bio-object autofluorescence. High efficiency in raising the temperature in the NSts environment with the irradiation of near infrared, AuNSts triggered photothermal effect. The decreased cell viability of A549 observed via MTT test and the cell membrane damaging was demonstrated with trypan blue staining. These results suggest AuNSts can be agents with tunable plasmonic properties for imaging and photothermal therapy.

Vibrational and electrochemical studies of pectin-a candidate towards environmental friendly lithium-ion battery development.

Pectin polymers are considered for lithium-ion battery electrodes. To understand the performance of pectin as an applied buffer layer, the electrical, magnetic, and optical properties of pectin films are investigated. This work describes a methodology for creating pectin films, including both pristine pectin and Fe-doped pectin, which are optically translucent, and explores their potential for lithium-ion battery application. The transmission response is found extended in optimally Fe-doped pectin, and prominent modes for cation bonding are identified. Fe doping enhances the conductivity observed in electrochemical impedance spectroscopy, and from the magnetic response of pectin evidence for Fe3+ is identified. The Li-ion half-cell prepared with pectin as binder for anode materials such as graphite shows stable charge capacity over long cycle life, and with slightly higher specific capacity compare with the cell prepared using polyvinylidene fluoride (PVDF) as binder. A novel enhanced charging specific capacity at a high C-rate is observed in cells with pectin binder, suggesting that within a certain rate (∼5 C), pectin has higher capacity at faster charge rates. The pectin system is found as a viable base material for organic-inorganic synthesis studies.

Raman Spectroscopic Study of TiO2 Nanoparticles' Effects on the Hemoglobin State in Individual Red Blood Cells.

Titanium dioxide (TiO2) is considered to be a nontoxic material and is widely used in a number of everyday products, such as sunscreen. TiO2 nanoparticles (NP) are also considered as prospective agents for photodynamic therapy and drug delivery. These applications require an understanding of the potential effects of TiO2 on the blood system and its components upon administration. In the presented work, we analyze the interaction of TiO2 nanoparticles of different crystal phases (anatase and rutile) with individual rat Red Blood Cells (RBC) and the TiO2 influence on the oxygenation state and functionality of RBC, estimated via analysis of Raman spectra of Hemoglobin (Hb) and their distribution along individual RBC. Raman spectral signals also allow localization of the TiO2 NP on the RBC. No penetration of the NP inside RBC was observed; however, both kinds of TiO2 NP adsorbed on the RBC membrane can affect the Hb state. Mechanisms involving the NP-membrane-Hb interaction, resulting in partial deoxygenation of Hb and TiO2 photothermal effect on Hb under Raman laser excitation, are suggested. The possible influence on the safety of TiO2 use in advanced medical application, especially on the safety and efficiency of photothermal therapy, is discussed.

Opportunistic gill infection is associated with TiO2 nanoparticle-induced mortality in zebrafish.

The large amounts of engineered titanium dioxide nanoparticles (TiO2NPs) that have been manufactured have inevitably been released into the ecosystem. Reports have suggested that TiO2 is a relatively inert material that has low toxicity to animals. However, as various types of NPs increasingly accumulate in the ocean, their effects on aquatic life-forms remain unclear. In this study, a zebrafish model was used to investigate TiO2NP-induced injury and mortality. We found that the treatment dosages of TiO2NP are positively associated with increased motility of zebrafish and the bacterial counts in the water. Notably, gill but not dorsal fin and caudal fin of the zebrafish displayed considerably increased bacterial load. Metagenomic analysis further revealed that gut microflora, such as phyla Proteobacteria, Bacteroidetes, and Actinobacteria, involving more than 95% of total bacteria counts in the NP-injured zebrafish gill samples. These results collectively suggest that opportunistic bacterial infections are associated with TiO2NP-induced mortality in zebrafish. Infections secondary to TiO2NP-induced injury could be a neglected factor determining the detrimental effects of TiO2NPs on wild fish.

Room Temperature Magnetic Memory Effect in Nanodiamond/γ-Fe2O3 Composites.

We report a room temperature magnetic memory effect (RT-MME) from magnetic nanodiamond (MND) (ND)/γ-Fe2O3 nanocomposites. The detailed crystal structural analysis of the diluted MND was performed by synchrotron radiation X-ray diffraction, revealing the composite nature of MND having 99 and 1% weight fraction ND and γ-Fe2O3 phases, respectively. The magnetic measurements carried out using a DC SQUID magnetometer show the non-interacting superparamagnetic nature of γ-Fe2O3 nanoparticles in MND have a wide distribution in the blocking temperature. Using different temperature, field, and time relaxation protocols, the memory phenomenon in the DC magnetization has been observed at room temperature (RT). These findings suggest that the dynamics of MND are governed by a wide distribution of particle relaxation times, which arise from the distribution of γ-Fe2O3 nanoparticle size. The observed RT ferromagnetism coupled with MME in MND will find potential applications in ND-based spintronics.

A review of recent advances in nanodiamond-mediated drug delivery in cancer.

INTRODUCTION: Nanodiamond (ND) refers to diamond particles with sizes from few to near 100 nanometers. For its superb physical, chemical and spectroscopic properties, it has been proposed and studied with the aims for bio imaging and drug delivery. Many modalities on conjugating drug molecules on ND to form ND-X for more efficient drug delivery have been demonstrated in the cellular and animal models. AREA COVERED: Many novel drug delivery approaches utilizing nanodiamond as a platform have been demonstrated recently. This review summarizes recent developments on the nanodiamond facilitated drug delivery, from the ND-X complexes preparations to tests in the cellular and animal models. The outlook on clinical translation is discussed. EXPERT OPINION: Nanodiamond and drug complexes (ND-X) produced from different methods are realized for drug delivery; almost all studies reported ND-X being more efficient compared to pure drug alone. However, ND of particle size less than 10 nm are found more toxic due to size and surface structure, and strongly aggregate. In vivo studies demonstrate ND accumulation in animal organs and no confirmed long-term effect studies on their release from organs are available. Standardized nanodiamond materials and drug delivery approaches are needed to advance the applications to the clinical level.

Phase transformation and room temperature stabilization of various Bi2O3 nano-polymorphs: effect of oxygen-vacancy defects and reduced surface energy due to adsorbed carbon species.

We report the grain growth from the nanoscale to microscale and a transformation sequence from Bi →ß-Bi2O3→γ-Bi2O3→α-Bi2O3 with the increase of annealing temperature. The room temperature (RT) stabilization of ß-Bi2O3 nanoparticles (NPs) was attributed to the effect of reduced surface energy due to adsorbed carbon species, and oxygen vacancy defects may have played a significant role in the RT stabilization of γ-Bi2O3 NPs. An enhanced red emission band was evident from all the samples attributed to oxygen-vacancy defects formed during the growth process in contrast with the observed white emission band from the air annealed Bi ingots. Based on our experimental findings, the air annealing induced oxidation of Bi NPs and transformation mechanism within various Bi2O3 nano-polymorphs are presented. The outcome of this study suggests that oxygen vacancy defects at the nanoscale play a significant role in both structural stabilization and phase transformation within various Bi2O3 nano-polymorphs, which is significant from theoretical consideration.

Structural and Enhanced Optical Properties of Stabilized γ‒Bi2O3 Nanoparticles: Effect of Oxygen Ion Vacancies.

We report the synthesis of room temperature (RT) stabilized γ-Bi2O3 nanoparticles (NPs) at the expense of metallic Bi NPs through annealing in an ambient atmosphere. RT stability of the metastable γ-Bi2O3 NPs is confirmed using synchrotron radiation powder X-ray diffraction and Raman spectroscopy. γ-Bi2O3 NPs exhibited a strong red-band emission peaking at ~701 nm, covering 81% integrated intensity of photoluminescence spectra. Our findings suggest that the RT stabilization and enhanced red-band emission of γ‒Bi2O3 is mediated by excess oxygen ion vacancies generated at the octahedral O(2) sites during the annealing process.

Optical Studies of Nanodiamond-Tissue Interaction: Skin Penetration and Localization.

In this work, several optical-spectroscopic methods have been used to visualize and investigate the penetration of diamond nanoparticles (NPs) of various sizes (3-150 nm), surface structures and fluorescence properties into the animal skin in vitro. Murine skin samples have been treated with nanodiamond (ND) water suspensions and studied using optical coherence tomography (OCT), confocal and two-photon fluorescence microscopy and fluorescence lifetime imaging (FLIM). An analysis of the optical properties of the used nanodiamonds (NDs) enables the selection of optimal optical methods or their combination for the study of nanodiamond-skin interaction. Among studied NDs, particles of 100 nm in nominal size were shown to be appropriate for multimodal imaging using all three methods. All the applied NDs were able to cross the skin barrier and penetrate the different layers of the epidermis to finally arrive in the hair follicle niches. The results suggest that NDs have the potential for multifunctional applications utilizing multimodal imaging.

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

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.

Raman spectroscopy on live mouse early embryo while it continues to develop into blastocyst in vitro.

Laser based spectroscopic methods can be versatile tools in investigating early stage mammalian embryo structure and biochemical processes in live oocytes and embryos. The limiting factor for using the laser methods in embryological studies is the effect of laser irradiation on the ova. The aim of this work is to explore the optimal parameters of the laser exposure in Raman spectroscopic measurements applicable for studying live early embryos in vitro without impacting their developmental capability. Raman spectra from different areas of mouse oocytes and 2-cells embryos were measured and analyzed. The laser power and exposure time were varied and further embryo development was evaluated to select optimal conditions of the measurements. This work demonstrates safe laser irradiation parameters can be selected, which allow acquisition of Raman spectra suitable for further analysis without affecting the early mouse embryo development in vitro up to morphologically normal blastocyst. The estimation of living embryo state is demonstrated via analysis and comparison of the spectra from fertilized embryo with the spectra from unfertilized oocytes or embryos subjected to UV laser irradiation. These results demonstrate the possibility of investigating preimplantation mammalian embryo development and estimating its state/quality. It will have potential in developing prognosis of mammalian embryos in assisted reproductive technologies.

Role of cobalt cations in short range antiferromagnetic Co3O4 nanoparticles: a thermal treatment approach to affecting phonon and magnetic properties.

We report the phonon and magnetic properties of various well-stabilized Co3O4 nanoparticles. The net valence in cobalt (II)/(III) cation can be obtained by subtracting the Co2+ ions in tetrahedral interstices and Co3+ ions in the octahedral interstices, respectively, which will possess spatial inhomogeneity of its magnetic moment via Co2+ in tetrahedra and Co3+ in octahedral configurations in the normal spinel structure. Furthermore, the distribution of Co2+/Co3+ governed by various external (magnetic field and temperature) and internal (particle size and slightly distorted CoO6 octahedra) sources, have led to phenomena such as a large redshift of phonon-phonon interaction and short-range magnetic correlation in the inverse spinel structure. The outcome of our study is important in terms of the future development of magnetic semiconductor spintronic devices of Co3O4.

Positive zeta potential of nanodiamonds.

In this paper, the origin of positive zeta potential exhibited by nanodiamond particles is explained. Positive zeta potentials in nano-structured carbons can be explained by the presence of graphitic planes at the surface, which leave oxygen-free Lewis sites and so promotes the suppression of acidic functional groups. Electron Microscopy and Raman Spectroscopy have been used to show that positive zeta potential of nanodiamond is only exhibited in the presence of sp2 carbon at the surface.

Spectroscopic Ellipsometry of Nanocrystalline Diamond Film Growth.

With the retention of many of the unrivaled properties of bulk diamond but in thin-film form, nanocrystalline diamond (NCD) has applications ranging from micro-/nano-electromechanical systems to tribological coatings. However, with Young's modulus, transparency, and thermal conductivity of films all dependent on the grain size and nondiamond content, compositional and structural analysis of the initial stages of diamond growth is required to optimize growth. Spectroscopic ellipsometry (SE) has therefore been applied to the characterization of 25-75 nm thick NCD samples atop nanodiamond-seeded silicon with a clear distinction between the nucleation and bulk growth regimes discernable. The resulting presence of an interfacial carbide and peak in nondiamond carbon content upon coalescence is correlated with Raman spectroscopy, whereas the surface roughness and microstructure are in accordance with values provided by atomic force microscopy. As such, SE is demonstrated to be a powerful technique for the characterization of the initial stages of growth and hence the optimization of seeding and nucleation within films to yield high-quality NCD.

Nanodiamonds for Medical Applications: Interaction with Blood in Vitro and in Vivo.

Nanodiamonds (ND) have emerged to be a widely-discussed nanomaterial for their applications in biological studies and for medical diagnostics and treatment. The potentials have been successfully demonstrated in cellular and tissue models in vitro. For medical applications, further in vivo studies on various applications become important. One of the most challenging possibilities of ND biomedical application is controllable drug delivery and tracing. That usually assumes ND interaction with the blood system. In this work, we study ND interaction with rat blood and analyze how the ND surface modification and coating can optimize the ND interaction with the blood. It was found that adsorption of a low concentration of ND does not affect the oxygenation state of red blood cells (RBC). The obtained in vivo results are compared to the results of in vitro studies of nanodiamond interaction with rat and human blood and blood components, such as red blood cells and blood plasma. An in vivo animal model shows ND injected in blood attach to the RBC membrane and circulate with blood for more than 30 min; and ND do not stimulate an immune response by measurement of proinflammatory cytokine TNF-α with ND injected into mice via the caudal vein. The results further confirm nanodiamonds' safety in organisms, as well as the possibility of their application without complicating the blood's physiological conditions.