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Nanoscale ; 12(44): 22754-22767, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33174556


Oral route is one of the most important portals of nanoparticle entry to the body. However, in vivo protein corona formed in the gastrointestinal tract has not been studied owing to the difficulty for the recovery of nanoparticles from the in vivo environment. In this study, by using the magnetic property of iron oxide nanoparticles (Fe3O4 NPs) and Zn2+ doped iron oxide nanoparticles (Zn0.4Fe2.6O4 NPs), the nanoparticles were separated from the gastric fluid after oral administration in mice. The effects of Zn2+ doping and static magnetic field (SMF) treatment on the protein adsorption on the nanoparticles were investigated in vitro and in vivo. Zn2+ doping decreases the adsorption of pepsin on the nanoparticles in vitro and affects the composition of the protein corona in vivo and enhances protein adsorption-induced aggregation of the nanoparticles in vitro and in vivo. SMF treatment affects the composition of the protein corona of Fe3O4 NPs and Zn0.4Fe2.6O4 NPs, and enhances the aggregation of Fe3O4 NPs and Zn0.4Fe2.6O4 NPs in vivo. Furthermore, the results demonstrate that electrostatic attraction is the crucial force to drive adsorption of proteins on Fe3O4 NPs and Zn0.4Fe2.6O4 NPs and protein adsorption-induced change in the surface charge of nanoparticles plays an important role in the pH-dependent aggregation of the nanoparticles. In addition, the work provides the evidence that the protein adsorption-induced aggregation of Fe3O4 NPs and Zn0.4Fe2.6O4 NPs has no effect on their magnetic susceptibility. The results highlight that Zn0.4Fe2.6O4 NPs may be used as a potential oral magnetic resonance imaging contrast agent in diagnosis of gastrointestinal disease.

Environ Pollut ; 258: 113758, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31881510


Natural halloysite nanotubes (HNTs) with a hollow lumen are already applied in numerous fields and enter the environment in increasing quantities, which may have effects on animal and human health. However their in vivo toxicity in mammals is still largely unclear. The aim of this study is to assess acute oral toxicity of HNTs in the stomach of mice and recovery. Oral HNTs at low dose (5 mg HNTs/kg BW) for 30 days increased in daily food and water intake and promoted mouse growth with no obvious adverse effect on the stomach. The promotive effect on mouse growth disappeared after cessation of oral administration of the nanotubes. Oral HNTs for 30 days at high dose (50 mg HNTs/kg BW) induced Si and Al accumulation in the stomach, which caused oxidative stress, inflammation and iNOS-mediated damage in the organ. The damage in the stomach led to slight atrophic gastritis and reduced mouse growth. Oral HNTs-induced changes at high dose were not observed after a 30-days recovery period. The findings provided the evidence that oral HNTs-induced acute toxicity in the stomach was reversible. More importantly, this research showed that Al and Si were cleared out of the mice by hepatic excretion and renal excretion, respectively, during the recovery period. The results suggest that HNTs at low concentration in environments have no adverse effect on mice, while there are health risks to mice under severe contamination by HNTs.

Argila , Nanotubos/toxicidade , Óxido Nítrico Sintase Tipo II/metabolismo , Estômago/enzimologia , Administração Oral , Alumínio , Animais , Camundongos , Estresse Oxidativo , Silício , Estômago/efeitos dos fármacos , Testes de Toxicidade Aguda
Biomaterials ; 224: 119478, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31542517


The Liver is the most common organ for metastasis for various cancers, including uveal melanoma, the most common primary intraocular tumor. Uveal melanoma metastasizes to the liver in ~90% of patients, and results in death in almost all cases due to late detection and lack of effective treatment. There is a pressing unmet medical need to develop MRI contrast agents and imaging methodologies with desired sensitivity and specificity to overcome the high heterogeneous background and in vivo properties as well as reduced toxicity. Herein, we report the development of a collagen targeting protein contrast agent (ProCA32.collagen1), since collagen is a diagnostic biomarker and therapeutic target for many types of primary and metastatic cancers and the tumor microenvironment. In addition to a strong affinity to collagen I, ProCA32.collagen1 possesses high relaxivities (r1 and r2 are 68.0 ±â€¯0.25 and 100.0 ±â€¯0.32 mM-1 s-1 at 1.4 T, respectively, and 42.6 ±â€¯1.0 and 217 ±â€¯2.4 mM-1s-1 at 7.0 T per particle). ProCA32.collagen1 also has strong serum stability against degradation, resistance to transmetallation, and 102 and 1013-fold higher metal selectivity for Gd3+ over Ca2+ and Zn2+, respectively, compared to clinical contrast agents. ProCA32.collagen1 does not exhibit any cell toxicity for various cell lines. Sensitive detection of liver lesions in animal models can be achieved using multiple imaging methodologies, taking advantage of the dual relaxation property of ProCA32.collagen1. ProCA32.collagen1 enables sensitive and early stage detection of hepatic micrometastasis as small as 0.144 mm2 and two different tumor growth patterns. Further development of ProCA32.collagen1 has the potential to greatly facilitate non-invasive, early detection and staging of primary and metastatic liver cancers, and devising effective treatments.

Colágeno/química , Meios de Contraste/química , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Imagem por Ressonância Magnética , Animais , Linhagem Celular , Sobrevivência Celular , Endocitose , Feminino , Humanos , Fígado/patologia , Camundongos Endogâmicos C57BL , Distribuição Tecidual
Environ Toxicol ; 33(6): 623-630, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29457689


Halloysite (Al2 Si2 O5 (OH)4 ·nH2 O) nanotubes (HNTs) are natural clay materials and widely applied in many fields due to their natural hollow tubular structures. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility, however the in vivo toxicity of HNTs remains unclear. The objective of this study was to assess the hepatic toxicity of the purified HNTs in mice via oral route. The purified HNTs were orally administered to mice at 5, 50, and 300 mg/kg body weight (BW) every day for 30 days. Oral administration of HNTs stimulated the growth of the mice at the low dose (5 mg/kg BW) with no liver toxicity, but inhibited the growth of the mice at the middle (50 mg/kg BW) and high (300 mg/kg BW) doses. In addition, oral administration of HNTs at the high dose caused Al accumulation in the liver but had no marked effect on the Si content in the organ. The Al accumulation caused significant oxidative stress in the liver, which induced hepatic dysfunction and histopathologic changes. These findings demonstrated that Al accumulation-induced oxidative stress played an important role in the oral HNTs-caused liver injury.

Silicatos de Alumínio/toxicidade , Alumínio/farmacocinética , Fígado/efeitos dos fármacos , Nanotubos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Administração Oral , Silicatos de Alumínio/administração & dosagem , Silicatos de Alumínio/química , Silicatos de Alumínio/farmacocinética , Animais , Argila , Dano ao DNA/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Nanotubos/química , Fatores de Tempo , Testes de Toxicidade Crônica
J Agric Food Chem ; 66(11): 2925-2933, 2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29470912


Natural halloysite (Al2Si2O5(OH)4· nH2O) nanotubes (HNT) are clay materials with hollow tubular structure and are widely applied in many fields. Many in vitro studies indicate that HNTs exhibit a high level of biocompatibility; however, the in vivo toxicity of HNTs remains unclear. In this study, the biodistribution and pulmonary toxicity of the purified HNTs in mice were investigated after intragastric administration for 30 days. HNTs have high stability in biological conditions. Oral administration of HNTs caused significant Al accumulation predominantly in the lung with relative slight effects on Si biodistribution. Oral administration of HNTs stimulated the growth of the mice at low dose (5 mg/kg BW) with no pulmonary toxicity but inhibited the mouse growth and resulted in oxidative stress and inflammation in lung at high dose (50 mg/kg BW). In addition, oral HNTs at high dose could be absorbed from the gastrointestinal tract and deposited in lung and could also induce pulmonary fibrosis.

Silicatos de Alumínio/metabolismo , Silicatos de Alumínio/toxicidade , Alumínio/toxicidade , Pulmão/efeitos dos fármacos , Camundongos/metabolismo , Nanotubos/toxicidade , Alumínio/metabolismo , Animais , Argila , Pulmão/metabolismo , Masculino , Camundongos/crescimento & desenvolvimento , Estresse Oxidativo , Distribuição Tecidual