Detonation nanodiamonds have found numerous potential applications in a diverse array of fields such as biomedical imaging and drug delivery. Here, we systematically characterized non-functionalized ...and polyglycerol-functionalized detonation nanodiamond particles (DNPs) dispersed in aqueous suspensions at different ionic strengths (∼1.0 × 10
to 1.0 × 10
M) via dynamic light scattering and cryogenic transmission electron microscopy. For these colloidal suspensions, the total potential energies of interactions between a pair of DNPs were theoretically calculated using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory plus the fitting of the Boltzmann distribution to the interparticle spacing distribution of the colloidal DNPs. These investigations revealed that the non-functionalized DNPs are dispersed in aqueous media through the long-range (>10 nm) and weak (<7
) electrical double-layer repulsive interaction, while the driving force on dispersion of polyglycerol-functionalized DNPs is mostly derived from the short-range (<2 nm) and strong (∼55
) steric repulsive potential barrier generated by the polyglycerol. Moreover, our results show that the truly monodispersed and individually dispersed DNP colloids, forming no aggregates in aqueous suspensions, are available by both functionalizing DNPs by polyglycerol and increasing ionic strength of suspending media to ≳1.0 × 10
M.
Silicon vacancy (SiV) color centers in diamond have attracted widespread attention owing to their stable photoluminescence (PL) with a sharp emission band in the near-infrared region (ZPL 738 nm). ...Especially, SiV center containing single-digit nanometer-sized nanodiamonds (single-digit SiV-NDs) are desirable for various applications such as bioimaging and biosensing because of their extremely small size, comparable to many biomaterials. Therefore, several attempts have been made to fabricate the single-digit SiV-NDs. However, there are no reports on the successful fabrication of such materials in reasonable scale of production. Here, we report the successful synthesis of single-digit SiV-NDs via straightforward detonation process, which is known to have the high productivity in fabrication of single-digit NDs. Triphenylsilanol (TPS), as a silicon source, was mixed with explosives (TPS/TNT/RDX = 1/59/40 wt%) and the detonation process was carried out. The obtained single-digit NDs exhibit PL at approximately 738 nm, indicating that single-digit SiV-NDs were successfully synthesized. Moreover, we conjectured that the physics behind this achievement may be attributed to the aromatic ring of TPS under the consideration of ND formation mechanism newly built up based on the results of time-resolved optical emission measurements for the detonation reaction.
Display omitted
•SiV centers in diamond are provided for various bioapplications.•SiV center-containing single-digit nanometer NDs were synthesized directly by detonation process.•Detonation with triphenylsilanol as a silicon source allowed to incorporate SiV centers into DNDs.•SiV centers in DNDs showed sharp PL emission peak centered at the ZPL = 738 nm.•Optical measurement of the detonation reaction revealed the physics behind the creation of SiV centers.
A nanodiamond (ND) is a promising material for drug delivery applications owing to its relatively low cost, amenability to large-scale synthesis, unique structure, and low toxicity. However, ...synthesizing drug-loaded ND conjugates with uniform and tunable sizes, high loading capacity, efficacy in drug delivery, and versatility in terms of surface functionalization has been challenging. Here, we show that perfluorooctanoic acid-functionalized NDs spontaneously transform into well-dispersed and biocompatible supraparticle (SP) nanoclusters. We demonstrate that the synthesized ND-based SPs (ND-SPs) exhibit high penetration through the cell membrane and are therefore superior as drug carriers for conventional nanomedicines such as polyethylene glycol and phospholipid-based nanocapsules and simple drug-loaded ND conjugates. We confirm the efficacy of ND-SPs in the eradication of cancer cells in vitro and in vivo. Our results demonstrate that the synthesized ND-SPs are useful for targeted drug delivery in a variety of biological applications.
High invasiveness is a characteristic of glioblastoma (GBM), making radical resection almost impossible, and thus, resulting in a tumor with inevitable recurrence. GBM recurrence may be caused by ...glioma stem-like cells (GSCs) that survive many kinds of therapy. GSCs with high expression levels of CD44 are highly invasive and resistant to radio-chemotherapy. CD44 is a multifunctional molecule that promotes the invasion and proliferation of tumor cells via various signaling pathways. Among these, paired pathways reciprocally activate invasion and proliferation under different hypoxic conditions. Severe hypoxia (0.5–2.5% O2) upregulates hypoxia-inducible factor (HIF)-1α, which then activates target genes, including CD44, TGF-β, and cMET, all of which are related to tumor migration and invasion. In contrast, moderate hypoxia (2.5–5% O2) upregulates HIF-2α, which activates target genes, such as vascular endothelial growth factor (VEGF)/VEGFR2, cMYC, and cyclin D1. All these genes are related to tumor proliferation. Oxygen environments around GBM can change before and after tumor resection. Before resection, the oxygen concentration at the tumor periphery is severely hypoxic. In the reparative stage after resection, the resection cavity shows moderate hypoxia. These observations suggest that upregulated CD44 under severe hypoxia may promote the migration and invasion of tumor cells. Conversely, when tumor resection leads to moderate hypoxia, upregulated HIF-2α activates HIF-2α target genes. The phenotypic transition regulated by CD44, leading to a dichotomy between invasion and proliferation according to hypoxic conditions, may play a crucial role in GBM recurrence.
We previously reported that glioma stemlike cells (GSCs) exist in the area of the tumor periphery showing no gadolinium enhancement on magnetic resonance imaging. In the present work, we analyzed ...glucose metabolism to investigate whether lactate could be predictive of tumor invasiveness and of use in detection of the tumor invasion area in glioblastoma multiforme (GBM).
The expression of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase (PDH) was investigated in 20 patients. In GSC lines, LDH-A and PDH expression also was examined in parallel to assessments of mitochondrial respiration. We then investigated the relationship between lactate/creatine ratios in the tumor periphery measured by magnetic resonance spectroscopy, using learning-compression-model algorithms and phenotypes of GBMs.
In 20 GBMs, high-invasive GBM expressed LDH-A at significantly higher expression than did low-invasive GBM, whereas low-invasive GBM showed significantly higher expression of PDH than did high-invasive GBM. The highly invasive GSC line showed higher expression of LDH-A and lower expression of PDH compared with low-invasive GSC lines. The highly invasive GSC line also showed the lowest consumption of oxygen and the lowest production of adenosine triphosphate. Lactate levels, as measured by magnetic resonance spectroscopy, showed a significant positive correlation with LDH-A transcript levels, permitting classification of the GBMs into high-invasive and low-invasive phenotypes based on a cutoff value of 0.66 in the lactate/creatine ratio.
In the tumor periphery area of the highly invasive GBM, aerobic glycolysis was the predominant pathway for glucose metabolism, resulting in the accumulation of lactate. The level of lactate may facilitate prediction of the tumor-infiltrating area on GBM.
Background
Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The ...present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS).
Methods
Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated.
Results
In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p < 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were > 1.25, > 1.09, and > 0.88, respectively.
Conclusions
Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.
PDF
