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1.
Nat Nanotechnol ; 16(6): 708-716, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33603238

RESUMO

Many nanoscale biomaterials fail to reach the clinical trial stage due to a poor understanding of the fundamental principles of their in vivo behaviour. Here we describe the transport, transformation and bioavailability of MoS2 nanomaterials through a combination of in vivo experiments and molecular dynamics simulations. We show that after intravenous injection molybdenum is significantly enriched in liver sinusoid and splenic red pulp. This biodistribution is mediated by protein coronas that spontaneously form in the blood, principally with apolipoprotein E. The biotransformation of MoS2 leads to incorporation of molybdenum into molybdenum enzymes, which increases their specific activities in the liver, affecting its metabolism. Our findings reveal that nanomaterials undergo a protein corona-bridged transport-transformation-bioavailability chain in vivo, and suggest that nanomaterials consisting of essential trace elements may be converted into active biological molecules that organisms can exploit. Our results also indicate that the long-term biotransformation of nanomaterials may have an impact on liver metabolism.


Assuntos
Dissulfetos/farmacocinética , Molibdênio/química , Molibdênio/farmacocinética , Nanoestruturas/química , Administração Intravenosa , Animais , Apolipoproteínas E/genética , Disponibilidade Biológica , Biotransformação , Proteínas Sanguíneas/metabolismo , Dissulfetos/análise , Feminino , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Simulação de Dinâmica Molecular , Molibdênio/análise , Molibdênio/sangue , Nanoestruturas/administração & dosagem , Coroa de Proteína/química , Coroa de Proteína/metabolismo , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Baço/citologia , Baço/efeitos dos fármacos , Distribuição Tecidual
2.
Nanotoxicology ; 15(1): 131-144, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33370537

RESUMO

The increasing emergence of nano-cosmetics in the marketplace provokes safety concerns with respect to percutaneous permeation and toxicity of nanomaterials inside the human body. In this study, in vivo percutaneous permeation and dermal safety of cosmetic cream containing Au nanosheets and extracted Au nanosheets from cosmetic creams are investigated with guinea pigs. Quantitative percutaneous permeation data suggests that Au nanosheets in cosmetic creams permeate into the skin epidermis, dermis, and subcutaneous layer after 10 d cutaneous exposure, but cannot enter the systemic circulation. However, more Au nanosheets are accumulated in the skin and the permeation of Au nanosheets increased after embedded into the cream matrix. Synchrotron radiation X-ray fluorescence (SRXRF) imaging reveals that Au nanosheets in cosmetics penetrate mainly through hair follicles in a time-dependent manner. Cosmetic creams rather than extracted Au nanosheets decrease the cell viability of keratinocytes and slightly induce apoptosis/necrosis of keratinocytes and skin dermal fibroblasts. Intriguingly, the growth of hair is inhibited by the cosmetic cream and the extracted Au nanosheets revealed by HE staining and immunohistochemistry (IHC) assay. Altogether this study provides insights into the comprehensive understanding of percutaneous permeation and dermal safety of cosmetic creams containing Au nanosheets. This work provides reliable methods to study the skin permeation, biodistribution, and dermal safety of nano-cosmetics and reminds the community of the crucial need to combine the assays at molecular, cellular, and organ levels in nanotoxicology research.


Assuntos
Fibroblastos/efeitos dos fármacos , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Cosméticos/toxicidade , Cobaias , Humanos , Queratinócitos/efeitos dos fármacos , Permeabilidade , Pele , Absorção Cutânea , Distribuição Tecidual
3.
ACS Nano ; 14(5): 5529-5542, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32283010

RESUMO

Two-dimensional (2D) nanosheets (NSs) have a large surface area, high surface free energy, and ultrathin structure, which enable them to more easily penetrate biological membranes and promote adsorption of drugs and proteins. NSs are capable of adsorbing a large amount of blood proteins to form NSs-protein corona complexes; however, their inflammatory effects are still unknown. Therefore, we investigated the pro-inflammatory effect of 2D model nanosheet structures, molybdenum disulfide (MoS2), and the MoS2 NSs-protein complexes with four abundant proteins in human blood, i.e., human serum albumin (HSA), transferrin (Tf), fibrinogen (Fg), and immunoglobulin G (IgG). The interactions between the NSs and the proteins were analyzed by quantifying protein adsorption, determining binding affinity, and correlating structural changes in the protein corona with the uptake of NSs by macrophages and the subsequent inflammatory response. Although all of the NSs-protein complexes induced inflammation, IgG-coated and Fg-coated NSs triggered much stronger inflammatory effects by producing and releasing more cytokines. Among the four proteins, IgG possessed the highest proportion of ß-sheets and led to fewer secondary structure changes on the MoS2 nanosheets. This can facilitate uptake and produce a stronger pro-inflammatory response in macrophages due to the recognition of an NSs-IgG complex by Fc gamma receptors and the subsequent activation of the NF-κB pathways. Our results demonstrate that the blood protein components contribute to the inflammatory effects of nanosheets and provide important insights for the nanosafety evaluation and the rational design of nanomedicines in the future.


Assuntos
Nanoestruturas , Coroa de Proteína , Adsorção , Humanos , Molibdênio , Albumina Sérica Humana
4.
Sci Adv ; 5(9): eaax0937, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31523712

RESUMO

Carbonic anhydrase (CA) IX overexpresses exclusively on cell membranes of hypoxic tumors, regulating the acidic tumor microenvironment. Small molecules of CA inhibitor modified with short peptide successfully achieve CA IX-targeted self-assembly that localizes CA inhibitors on hypoxic cancer cell surfaces and enhances their inhibition efficacy and selectivity. CA IX-related endocytosis also promotes selective intracellular uptake of these nanofibers under hypoxia, in which nanofiber structures increase in size with decreasing pH. This effect subsequently causes intracellular acid vesicle damage and blocks protective autophagy. The versatility of tunable nanostructures responding to cell milieu impressively provokes selective toxicities and provides strategic therapy for hypoxic tumors. Moreover, in vivo tests demonstrate considerable antimetastatic and antiangiogenesis effects in breast tumors, and particularly remarkable enhancement of antitumor efficacy in doxorubicin administration. With its biocompatible components and distinctive hypoxia therapies, this nanomaterial advances current chemotherapy, providing a new direction for hypoxic cancer therapy.


Assuntos
Neoplasias da Mama , Inibidores da Anidrase Carbônica , Doxorrubicina , Nanofibras , Peptídeos , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Humanos , Camundongos , Camundongos Nus , Nanofibras/química , Nanofibras/uso terapêutico , Peptídeos/química , Peptídeos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Small ; 13(10)2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28009471

RESUMO

As a widely used nanomaterial in daily life, silver nanomaterials may cause great concern to female reproductive system as they are found to penetrate the blood-placental barrier and gain access to the ovary. However, it is largely unknown about how silver nanomaterials influence ovarian physiology and functions such as hormone production. This study performs in vitro toxicology study of silver nanomaterials, focusing especially on cytotoxicity and steroidogenesis and explores their underlying mechanisms. This study exposes primary rat granulosa cells to gold nanorod core/silver shell nanostructures (Au@Ag NRs), and compares outcomes with cells exposed to gold nanorods. The Au@Ag NRs generate more reactive oxygen species and reduce mitochondrial membrane potential and less production of adenosine triphosphate. Au@Ag NRs promote steroidogenesis, including progesterone and estradiol, in a time- and dose-dependent manner. Chemical reactivity and transformation of Au@Ag NRs are then studied by electron spin resonance spectroscopy and X-ray absorption near edge structure, which analyze the generation of free radical and intracellular silver species. Results suggest that both particle-specific activity and intracellular silver ion release of Au@Ag NR contribute to the toxic response of granulosa cells.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanoestruturas/química , Nanoestruturas/toxicidade , Nanotubos/química , Prata/química , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Ratos Sprague-Dawley
6.
Adv Mater ; 28(40): 8950-8958, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27562240

RESUMO

An original gadolinium-hybridized plasmonic gold nanocomposite is fabricated to provide an insightful and attractive strategy to overcome both the physiological and pathological barriers of tumor, and increase the transportation and permeability of imaging agents and drugs in tumor interior for achieving high-sensitive multimodal imaging and simultaneously improving the therapeutic efficacy of cancer.


Assuntos
Imagem Multimodal , Nanocompostos , Gadolínio , Ouro , Neoplasias , Permeabilidade
7.
Small ; 12(39): 5488-5496, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27562146

RESUMO

Establishment of analytical methods of engineered nanomaterials in consumer products for their human and environmental risk assessment becomes urgent for both academic and industrial needs. Owing to the difficulties and challenges around nanomaterials in complex media, proper chemical separation and biological assays of nanomaterials from nanoproducts needs to be firstly developed. Herein, a facile and rapid method to separate and analyze gold nanomaterials in cosmetics is reported. Gold nanomaterials are successfully separated from different facial or eye creams and their physiochemical properties are analyzed by quantitative and qualitative state-of-the art techniques with high sensitivity or high spatial resolution. In turn, a protocol including quantification of gold by inductively coupled plasma mass spectrometry and thorough characterization of morphology, size distribution, and surface property by electron microscopes, atomic force microscope, and X-ray photoelectron spectroscope is developed. Subsequently, the preliminary toxicity assessment indicates that gold nanomaterials in cosmetic creams have no observable toxicity to human keratinocytes even after 24 h exposure up to a concentration of 200 µg mL-1 . The environmental scanning electron microscope reveals that gold nanomaterials are mostly attached on the cell membrane. Thus, the present study provides a full analysis protocol for toxicity assessment of gold nanomaterials in consumer products (cosmetic creams).


Assuntos
Qualidade de Produtos para o Consumidor , Cosméticos , Ouro/análise , Nanoestruturas/análise , Medição de Risco , Pele/patologia , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/ultraestrutura , Microscopia de Força Atômica , Nanoestruturas/química , Nanoestruturas/toxicidade , Tamanho da Partícula , Espectroscopia Fotoeletrônica , Espectrometria por Raios X
8.
ACS Nano ; 10(4): 4587-98, 2016 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-27014806

RESUMO

A key challenge for the use of inorganic nanomedicines in clinical applications is their long-term accumulation in internal organs, which raises the common concern of the risk of adverse effects and inflammatory responses. It is thus necessary to rationally design inorganic nanomaterials with proper accumulation and clearance mechanism in vivo. Herein, we prepared ultrasmall Cu3BiS3 nanodots (NDs) as a single-phased ternary bimetal sulfide for photothermal cancer therapy guided by multispectral optoacoustic tomography (MSOT) and X-ray computed tomography (CT) due to bismuth's excellent X-ray attenuation coefficient. We then monitored and investigated their absorption, distribution, metabolism, and excretion. We also used CT imaging to demonstrate that Cu3BiS3 NDs can be quickly removed through renal clearance, which may be related to their small size, rapid chemical transformation, and degradation in an acidic lysosomal environment as characterized by synchrotron radiation-based X-ray absorption near-edge structure spectroscopy. These results reveal that Cu3BiS3 NDs act as a simple but powerful "theranostic" nanoplatform for MSOT/CT imaging-guided tumor ablation with excellent metabolism and rapid clearance that will improve safety for clinical applications in the future.


Assuntos
Antineoplásicos/farmacocinética , Bismuto/química , Cobre/química , Rim/metabolismo , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Sulfetos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células MCF-7 , Camundongos , Tamanho da Partícula , Técnicas Fotoacústicas , Fototerapia/métodos , Reabsorção Renal , Nanomedicina Teranóstica , Distribuição Tecidual , Tomografia Computadorizada por Raios X
9.
ACS Appl Mater Interfaces ; 7(45): 25014-23, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26418578

RESUMO

The combination of therapy and diagnosis has been emerging as a promising strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and magnetic resonance imaging (MRI) in one system, we have synthesized a new magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX), indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres (Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC coating serves as a polymer layer to protect from quick release of drugs from the nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG-PDC depends on pH and temperature. The process will be accelerated in the acidic condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the photothermal effects promote DOX release and improve the therapeutic efficacy compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can thus act as a promising theranostic platform for multimodal cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Quelantes/química , Gadolínio/química , Hipertermia Induzida , Nanosferas/química , Neoplasias/tratamento farmacológico , Fototerapia , Dióxido de Silício/química , Antineoplásicos/farmacologia , Morte Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Humanos , Raios Infravermelhos , Íons , Células MCF-7 , Imageamento por Ressonância Magnética , Nanosferas/ultraestrutura , Espectrofotometria Ultravioleta , Temperatura , Espectroscopia por Absorção de Raios X
10.
Chemistry ; 19(47): 16087-92, 2013 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-24123196

RESUMO

Pt-based nanostructures serving as anode catalysts for the methanol oxidation reaction (MOR) have been widely studied for many years. Nevertheless, challenging issues such as poor reaction kinetics and the short-term stability of the MOR are the main drawbacks of such catalysts and limit their applications. Herein, we have developed a facile approach to encapsulate Pt nanoparticles (NPs) inside the nanochannels of porous carbon nanotubes (CNTs; Pt-in-CNTs) as a new enhanced electrocatalytic material. The as-prepared CNTs offer simultaneously ordered diffusion channels for ions and a confinement effect for the NPs, which both facilitate the promotion of catalytic kinetics and avoid the Ostwald ripening of Pt NPs, thus leading to high activity and durable cycle life as an anode catalyst for MOR. This work provides a new approach for enhancing the stability and activity by optimizing the structure of the catalyst, and the Pt-in-CNTs represent the most durable catalysts ever reported for MOR.

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