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ABSTRACT: Recent development in nanotechnology has provided new tools for cancer therapy and diagnostics. Because of their small size,
nanoscale devices readily interact with biomolecules both on the cell surface and inside the cell. Nanomaterials, such as
fullerenes and their derivatives, are effective in terms of interactions with the immune system and have great potential as
anticancer drugs. Comparatively, other nanomaterials are able to load active drugs to cancer cells by selectively using the
unique tumor environment, such as their enhanced permeability, retention effect and the specific acidic microenvironment.
Multifunctional and multiplexed nanoparticles, as the next generation of nanoparticles, are now being extensively investigated
and are promising tools to achieve personalized and tailored cancer treatments.
Keywordsnanotechnology-nanomaterials-nanocarrier-cancer therapy-drug delivery-passive target-active target
Science China-Chemistry 04/2012; 53(11):2241-2249. · 1.02 Impact Factor
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ABSTRACT: With the development of nanotechnology and the wide use of graphene, it has become necessary to assess the potential biological adverse effects of graphene. However, most of the recent publications are focused on various modified graphenes. We demonstrated biological effects of commercial pristine graphene in murine RAW 264.7 macrophages, which is an important effector cells of the innate immune system. We found that the pristine graphene can induce cytotoxicity through the depletion of the mitochondrial membrane potential (MMP) and the increase of intracellular reactive oxygen species (ROS), then trigger apoptosis by activation of the mitochondrial pathway. The MAPKs (JNK, ERK and p38) as well as the TGF-beta-related signaling pathways were found to be activated in the pristine grapheme-treated cells, which activated Bim and Bax, two pro-apoptotic member of Bcl-2 protein family. Consequently, the caspase 3 and its downstream effector proteins such as PARP were activated and the execution of apoptosis was initiated. This study provides an insight for the suppression of the apoptosis induced by the graphene through the mitochondrial pathways, the MAPKs- and TGF-beta-related signaling pathways.
Biomaterials 01/2012; 33(2):402-11. · 7.40 Impact Factor
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Lili Zhang,
Ru Bai,
Bai Li,
Cuicui Ge,
Jiangfeng Du,
Ying Liu, Laurent Le Guyader,
Yuliang Zhao,
Yanchuan Wu,
Shida He,
Yongmei Ma,
Chunying Chen
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ABSTRACT: The rising commercial use and large-scale production of engineered nanoparticles (NPs) may lead to unintended exposure to humans. The central nervous system (CNS) is a potential susceptible target of the inhaled NPs, but so far the amount of studies on this aspect is limited. Here, we focus on the potential neurological lesion in the brain induced by the intranasally instilled titanium dioxide (TiO₂) particles in rutile phase and of various sizes and surface coatings. Female mice were intranasally instilled with four different types of TiO₂ particles (i.e. two types of hydrophobic particles in micro- and nano-sized without coating and two types of water-soluble hydrophilic nano-sized particles with silica surface coating) every other day for 30 days. Inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the titanium contents in the sub-brain regions. Then, the pathological examination of brain tissues and measurements of the monoamine neurotransmitter levels in the sub-brain regions were performed. We found significant up-regulation of Ti contents in the cerebral cortex and striatum after intranasal instillation of hydrophilic TiO₂ NPs. Moreover, TiO₂ NPs exposure, in particular the hydrophilic NPs, caused obvious morphological changes of neurons in the cerebral cortex and significant disturbance of the monoamine neurotransmitter levels in the sub-brain regions studied. Thus, our results indicate that the surface modification of the NPs plays an important role on their effects on the brain. In addition, the difference in neurotoxicity of the two types of hydrophilic NPs may be induced by the shape differences of the materials. The present results suggest that physicochemical properties like size, shape and surface modification of the nanomaterials should be considered when evaluating their neurological effects.
Toxicology Letters 08/2011; 207(1):73-81. · 3.23 Impact Factor
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ABSTRACT: Increasing production and application of metallic nanomaterials are likely to result in the release of these particles into the environment. These released nanoparticles may enter into the lungs and the central nervous system (CNS) directly through inhalation, which therefore poses a potential risk to human health. Herein, we focus on the systemic toxicity and potential influence on the neurotransmitter secretion of intranasally instilled copper nanoparticles (23.5 nm) at three different doses. Copper nanoparticle-exposed mice exhibit pathological lesions at different degrees in certain tissues and especially in lung tissue as revealed by histopathology and transmission electron microscopy (TEM) observations. Inductively-coupled plasma mass spectrometry (ICP-MS) results show that the liver, lung and olfactory bulb are the main tissues in which the copper concentrations increased significantly after exposure to a higher level of Cu nanoparticles (40 mg/kg of body weight). The secretion levels of various neurotransmitters changed as well in some brain regions, especially in the olfactory bulb. Our results indicate that the intranasally instilled copper nanoparticles not only cause the lesions where the copper accumulates, but also affect the neurotransmitter levels in the brain.
Nanotoxicology 06/2011; 6(5):562-75. · 5.76 Impact Factor
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ABSTRACT: The release of ultrafine particles from office equipment is currently receiving great concerns due to its potential threat to human health when inhaled. Printer toner is one of the largest consumables in daily office work, and the particles released from printers and photocopiers may pose damage to respiratory system. In this study, we found the particles can be released into the surrounding environment during the printing process and the concentrations of PM(2.5) and PM(10) particles increased obviously. To evaluate the time-course pulmonary responses caused by toner particles, the toner suspension was instilled into the lungs of the male mice through intratracheally instillation every other day for four times and the pulmonary responses of the lung were monitored at days 9, 28, 56 and 84. Indeed, mice treated with toner particles displayed a slower body weight growth rate during the recovery phase. The total cell number in bronchoalveolar lavage fluids (BALF) of toner-exposed groups was much higher than the saline-treated groups. The total protein, lactate dehydrogenase and acid phosphatase in BALF exhibited significant changes (p<0.05 or p<0.01) at different time points. The nitric oxide synthase, interleukin 1-beta, and interleukin 6 in the lung tissue of the toner-exposed groups also exhibited significant changes (p<0.05 or p<0.01). The pathological examination showed that toner particles can adhere to the alveolar septal walls, then enter into the alveoli and cause pulmonary lesion. During the experimental period, particles phagocytosed by alveolar macrophages (AMs) led to an increase of both AMs number and apoptosis. The pulmonary stress still remained over time even with a clearance period for 12 weeks. These results indicate that exposure to toner particles can inhibit the normal growth of the mice and induce significant inflammatory responses and lesion in the lung tissues. The health and safety effects from working indoors in offices with fumes and particles released from photocopiers and printers need to be paid more attention.
Toxicology Letters 09/2010; 199(3):288-300. · 3.23 Impact Factor
