Abstract The present study compared the photothermal anticancer activity of near-infrared (NIR)-excited graphene nanoparticles and carbon nanotubes (CNT). Despite lower NIR-absorbing capacity, ...suspension of polyvinylpyrrolidone-coated graphene sheets exposed to NIR radiation (808 nm, 2 W/cm2 ) generated more heat than DNA or sodium dodecylbenzenesulfonate-solubilized single-wall CNT under the same conditions. Accordingly, graphene nanoparticles performed significantly better than CNT in inducing photothermal death of U251 human glioma cells in vitro. The superior photothermal sensitivity of graphene sheets could be largely explained by their better dispersivity, which has been supported by a simple calculation taking into account thermodynamic, optical and geometrical properties of the two type of carbon nanoparticles. The mechanisms of graphene-mediated photothermal killing of cancer cells apparently involved oxidative stress and mitochondrial membrane depolarization resulting in mixed apoptotic and necrotic cell death characterized by caspase activation/DNA fragmentation and cell membrane damage, respectively.
Abstract Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced ...graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli . Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD.
Abstract The excellent photoluminescent properties of graphene quantum dots (GQD) makes them suitable candidates for biomedical applications, but their cytotoxicity has not been extensively studied. ...Here we show that electrochemically produced GQD irradiated with blue light (470 nm, 1 W) generate reactive oxygen species, including singlet oxygen, and kill U251 human glioma cells by causing oxidative stress. The cell death induced by photoexcited GQD displayed morphological and/or biochemical characteristics of both apoptosis (phosphatidylserine externalization, caspase activation, DNA fragmentation) and autophagy (formation of autophagic vesicles, LC3-I/LC3-II conversion, degradation of autophagic target p62). Moreover, a genetic inactivation of autophagy-essential LC3B protein partly abrogated the photodynamic cytotoxicity of GQD. These data indicate potential usefulness of GQD in photodynamic therapy, but also raise concerns about their possible toxicity.
Abstract The influence of fullerene (C60 ) nanoparticles on the cytotoxicity of a highly reactive free radical nitric oxide (NO) was investigated. Fullerene nanoparticles were prepared by ...mechanochemically assisted complexation with anionic surfactant sodium dodecyl sulfate, macrocyclic oligosaccharide γ-cyclodextrin or the copolymer ethylene vinyl acetate–ethylene vinyl versatate. C60 nanoparticles were characterized by UV–vis and atomic force microscopy. While readily internalized by mouse L929 fibroblasts, C60 nanoparticles were not cytotoxic. Moreover, they partially protected L929 cells from the cytotoxic effect of NO-releasing compounds sodium nitroprusside (SNP), S-nitroso- N -acetylpenicillamine (SNAP), S-nitrosoglutathione (GSNO) and 3-morpholino-sydnonimine (SIN-1). C60 nanoparticles reduced SNP-induced apoptotic cell death by preventing mitochondrial depolarization, caspase activation, cell membrane phosphatidylserine exposure and DNA fragmentation. The protective action of C60 nanoparticles was not exerted via direct interaction with NO, but through neutralization of mitochondria-produced superoxide radical in NO-treated cells, as demonstrated by using different redox-sensitive reporter fluorochromes. These data suggest that C60 complexes with appropriate host molecules might be plausible candidates for preventing NO-mediated cell injury in inflammatory/autoimmune disorders.
Abstract In the present study, we compared the effects of nanocrystalline fullerene suspension (nanoC60 ) on tumour cell growth in vitro and in vivo. NanoC60 suspension was prepared by solvent ...exchange using tetrahydrofuran to dissolve C60 . In vitro, nanoC60 caused oxidative stress, mitochondrial depolarization and caspase activation, leading to apoptotic and necrotic death in mouse B16 melanoma cells. Biodistribution studies demonstrated that intraperitoneally injected radiolabeled (125 I) nanoC60 readily accumulated in the tumour tissue of mice subcutaneously inoculated with B16 cells. However, intraperitoneal administration of nanoC60 over the course of two weeks starting from melanoma cell implantation not only failed to reduce, but significantly augmented tumour growth. The tumour-promoting effect of nanoC60 was accompanied by a significant increase in splenocyte production of the immunoregulatory free radical nitric oxide (NO), as well as by a reduction in splenocyte proliferative responses to T- and B-cell mitogens ConcanavalinA and bacterial lipopolysaccharide, respectively. A negative correlation between NO production and splenocyte proliferation indicated a possible role of NO in reducing the proliferation of splenocytes from nanoC60 -injected mice. These data demonstrate that nanoC60 , in contrast to its potent anticancer activity in vitro, can potentiate tumour growth in vivo, possibly by causing NO-dependent suppression of anticancer immune response.
The design, synthesis and biological evaluation of a novel C,D-spirolactone analogue of paclitaxel is described. This is the first paclitaxel analogue without an oxetane D-ring that shows a ...significant cytotoxic effect (activity one order of magnitude lower than paclitaxel). More importantly, its cytotoxicity is a result of a different mechanism of action, involving mTOR inhibition-dependent autophagy instead of G(2)/M cell cycle arrest-dependent apoptosis.
Cerebral small vessel disease is rarely described in association with pseudoxanthoma elasticum (PXE), a hereditary connective tissue disorder with skin, eye and vascular manifestations. This ...autosomally inherited elastic tissue disease has been attributed to mutations in the ABCC6 gene located on chromosome 16p13.1. Different stroke mechanisms are suggested in PXE patients, arterial hypertension and accelerated atherosclerosis being the leading ones.
Case 1: A 49-year-old man with history of mild hypertension presented with recurrent transient ischemic attacks. At the age of 42, evaluation for progressive visual loss and skin changes led to diagnosis of PXE. Brain magnetic resonance imaging (MRI) disclosed multiple lacunar infarctions and confluent periventricular white matter lesions (WML). Case 2: A 71-year-old woman with history of mild hypertension suffered right-sided stroke. Diagnosis of PXE was made at the age of 48 due to severe visual loss and skin changes. Brain MRI revealed multiple lacunar infarctions and subcortical ischemic leukoencephalopathy. Case 3: A 47-year-old woman with prominent skin changes and bilateral amblyopia developed right-sided weakness. Skin biopsy confirmed PXE. Several lacunar infarcts in deep white matter and pons were revealed on MRI.
We present three patients with clinical and histopathological features of PXE who presented with multiple lacunar strokes, two with extensive confluent WML. These cases illustrate that PXE is a rare but significant risk factor for small vessel disease and stroke in patients of all age groups. Occlusive small vessel disease and subsequent lacunar infarcts and WML represent important PXE manifestations.
In the present study, we compared the effects of nanocrystalline fullerene suspension (nanoC
60) on tumour cell growth in vitro and in vivo. NanoC
60 suspension was prepared by solvent exchange using ...tetrahydrofuran to dissolve C
60. In vitro, nanoC
60 caused oxidative stress, mitochondrial depolarization and caspase activation, leading to apoptotic and necrotic death in mouse B16 melanoma cells. Biodistribution studies demonstrated that intraperitoneally injected radiolabeled (
125I) nanoC
60 readily accumulated in the tumour tissue of mice subcutaneously inoculated with B16 cells. However, intraperitoneal administration of nanoC
60 over the course of two weeks starting from melanoma cell implantation not only failed to reduce, but significantly augmented tumour growth. The tumour-promoting effect of nanoC
60 was accompanied by a significant increase in splenocyte production of the immunoregulatory free radical nitric oxide (NO), as well as by a reduction in splenocyte proliferative responses to T- and B-cell mitogens ConcanavalinA and bacterial lipopolysaccharide, respectively. A negative correlation between NO production and splenocyte proliferation indicated a possible role of NO in reducing the proliferation of splenocytes from nanoC
60-injected mice. These data demonstrate that nanoC
60, in contrast to its potent anticancer activity in vitro, can potentiate tumour growth in vivo, possibly by causing NO-dependent suppression of anticancer immune response.
Small vessel disease (SVD) is associated with traditional vascular risk factors (RF). The aim of our study was to determine whether different SVD types, single lacunar infarction (LI) and multiple LI ...(MLI) with or without white matter lesions (WML), have different RF profiles.
Forty RF parameters were analysed in 201 consecutive patients with magnetic resonance imaging finding of SVD.
History of arterial hypertension, higher systolic and mean blood pressure (BP) but also hypotension, and higher plasma homocysteine levels were more frequent in MLI compared to single LI patients (p<0.05). Patients with one LI were younger, more frequently had clinically evident stroke and family history of cardiovascular disease (CVD) (p<0.05). Significant difference between groups was found only in these RF, indicating that similar pathological processes led to both types of SVD.
Positive correlation with age and family history of CVD necessitates further analyses of other factors, predominantly genetic, as the key to the answer why patients develop different lesions in SVD.
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