[PMID]: | 28420299 |
[Au] Autor: | Chandran P; Riviere JE; Monteiro-Riviere NA |
[Ad] Endereço: | a Department of Anatomy and Physiology, Nanotechnology Innovation Center of Kansas State , Kansas State University , Manhattan , KS , USA. |
[Ti] Título: | Surface chemistry of gold nanoparticles determines the biocorona composition impacting cellular uptake, toxicity and gene expression profiles in human endothelial cells. |
[So] Source: | Nanotoxicology;11(4):507-519, 2017 May. |
[Is] ISSN: | 1743-5404 |
[Cp] País de publicação: | England |
[La] Idioma: | eng |
[Ab] Resumo: | This study investigated the role of nanoparticle size and surface chemistry on biocorona composition and its effect on uptake, toxicity and cellular responses in human umbilical vein endothelial cells (HUVEC), employing 40 and 80 nm gold nanoparticles (AuNP) with branched polyethyleneimine (BPEI), lipoic acid (LA) and polyethylene glycol (PEG) coatings. Proteomic analysis identified 59 hard corona proteins among the various AuNP, revealing largely surface chemistry-dependent signature adsorbomes exhibiting human serum albumin (HSA) abundance. Size distribution analysis revealed the relative instability and aggregation inducing potential of bare and corona-bound BPEI-AuNP, over LA- and PEG-AuNP. Circular dichroism analysis showed surface chemistry-dependent conformational changes of proteins binding to AuNP. Time-dependent uptake of bare, plasma corona (PC) and HSA corona-bound AuNP (HSA-AuNP) showed significant reduction in uptake with PC formation. Cell viability studies demonstrated dose-dependent toxicity of BPEI-AuNP. Transcriptional profiling studies revealed 126 genes, from 13 biological pathways, to be differentially regulated by 40 nm bare and PC-bound BPEI-AuNP (PC-BPEI-AuNP). Furthermore, PC formation relieved the toxicity of cationic BPEI-AuNP by modulating expression of genes involved in DNA damage and repair, heat shock response, mitochondrial energy metabolism, oxidative stress and antioxidant response, and ER stress and unfolded protein response cascades, which were aberrantly expressed in bare BPEI-AuNP-treated cells. NP surface chemistry is shown to play the dominant role over size in determining the biocorona composition, which in turn modulates cell uptake, and biological responses, consequently defining the potential safety and efficacy of nanoformulations. |
[Mh] Termos MeSH primário: |
Células Endoteliais/efeitos dos fármacos Ouro Nanopartículas Metálicas Coroa de Proteína/metabolismo Transcriptoma/efeitos dos fármacos
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[Mh] Termos MeSH secundário: |
Albuminas/metabolismo Sobrevivência Celular/efeitos dos fármacos Dicroísmo Circular Células Endoteliais/metabolismo Ouro/química Ouro/toxicidade Células Endoteliais da Veia Umbilical Humana Seres Humanos Nanopartículas Metálicas/química Nanopartículas Metálicas/toxicidade Tamanho da Partícula Polietilenoglicóis/química Polietilenoimina/química Proteômica Propriedades de Superfície
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Albumins); 0 (Protein Corona); 30IQX730WE (Polyethylene Glycols); 7440-57-5 (Gold); 9002-98-6 (Polyethyleneimine) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 170929 |
[Lr] Data última revisão:
| 170929 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170420 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1080/17435390.2017.1314036 |
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