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Langmuir ; 35(45): 14688-14695, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31635450


Physicochemical properties of nanomaterials play important roles in determining their toxicological profiles during nano-biointeraction. Among them, surface modification is one of the most effective manners to tune the cytotoxicity induced by nanomaterials. However, currently, there is no consistency in surface modification including moiety types and quantities considering the conflicting toxicological profiles of particles across different studies. In this study, in order to systematically investigate how the moiety density affects cytotoxicity of NPs, we chose three different types of functional groups, that is, -NH2, -COOH, and -PEG, and further controlled their densities on modified Stöber silica nanoparticles (NPs). We demonstrated that densities of functional groups could significantly affect the cytotoxicities of Stöber silica NPs. Regardless of the types of functional groups, high grafting densities could ameliorate the cytotoxicities induced by Stöber silica NPs in macrophages, for example, J774A.1 and N9 cells. When equal amounts of functional groups were present, the cell viability increased in the order of -COOH < -NH2 < -PEG. Furthermore, it was shown that surface modification could significantly affect the quantities of the surface silanol, which is the determining factor that affects their cytotoxicity. These results show that it is critical to control the surface moiety both quantitatively and qualitatively, which can tune the interaction outcomes at the nano-bio interface. The results found in this article provide useful guidance to adjust nanomaterial cytotoxicity for safer biomedical applications.

Nanoscale ; 11(27): 12965-12972, 2019 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-31259344


With the wide application of Stöber silica nanoparticles and their ability to access the brain, it is crucial to evaluate their neurotoxicity. In this study, we used three in vitro model cells, i.e., N9, bEnd.3 and HT22 cells, representing microglia, microendothelial cells and neurons, respectively, to assess the neurotoxicity of Stöber silica nanoparticles with different sizes. We found that Stöber silica nanoparticles almost had no effect on the viability of bEnd.3 and HT22 cells. In contrast, they induced size-dependent toxicity in N9 cells, which represent the residential macrophages of the central nervous system. Further mechanistic study demonstrated that the toxicity in N9 cells was related to their surface silanol display. In addition, we demonstrated that Stöber silica nanoparticles induced the production of mitochondrial ROS, release of IL-1ß, cleavage of GSDMD, and occurrence of pyroptosis in N9 cells. Features of pyroptosis were also observed in primary microglia and macrophage J774A.1. In conclusion, these findings were helpful for the safety consideration of Stöber silica nanoparticles considering their wide applications in our daily life.

Microglia/metabolismo , Mitocôndrias/metabolismo , Nanopartículas/efeitos adversos , Piroptose/efeitos dos fármacos , Dióxido de Silício/efeitos adversos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Microglia/patologia , Mitocôndrias/patologia , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Dióxido de Silício/farmacologia
Int J Nanomedicine ; 14: 4167-4186, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239675


Engineered nanomaterials (ENMs) have been widely used in various fields due to their novel physicochemical properties. However, the use of ENMs has led to an increased exposure in humans, and the safety of ENMs has attracted much attention. It is universally acknowledged that ENMs could enter the human body via different routes, eg, inhalation, skin contact, and intravenous injection. Studies have proven that ENMs can cross or bypass the blood-brain barrier and then access the central nervous system and cause neurotoxicity. Until now, diverse in vivo and in vitro models have been developed to evaluate the neurotoxicity of ENMs, and oxidative stress, inflammation, DNA damage, and cell death have been identified as being involved. However, due to various physicochemical properties of ENMs and diverse study models in existing studies, it remains challenging to establish the structure-activity relationship of nanomaterials in neurotoxicity. In this paper, we aimed to review current studies on ENM-induced neurotoxicity, with an emphasis on the molecular and cellular mechanisms involved. We hope to provide a rational material design strategy for ENMs when they are applied in biomedical or other engineering applications.

Nanoestruturas/toxicidade , Nanotecnologia , Neurotoxinas/toxicidade , Morte Celular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/patologia , Dano ao DNA , Humanos , Nanoestruturas/química