Surface chemistry of gold nanoparticles determines the biocorona composition impacting cellular uptake, toxicity and gene expression profiles in human endothelial cells

Abstract

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. Timedependent 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. ARTICLE HISTORY

The Effects of Physicochemical Properties of Nanomaterials on Their Cellular Uptake In Vitro and In Vivo

“…By proteomic analysis on the surface chemistry‐dependent signature adsorbates, researchers find that human serum albumin (HSA) can more easily form corona on NMs surface than human plasma protein (HP). Time‐dependent cellular uptake detection shows that HSA corona‐bound gold nanoparticles have significant reduction in cellular uptake compared with HP corona‐bound ones . Another interesting report shows that gold‐based NMs with the same chemical composition but different surface modification have totally different cell membrane response.…”

Cytotoxicity-Related Bioeffects Induced by Nanoparticles: The Role of Surface Chemistry

“…In another study, the zeta potential of poly(diallyldimethyl ammonium chloride) (PDDAC), CTAB, and polystyrene sulfonate (PSS)decorated gold nanorods (GNRs) (33 × 30 and 55 × 14 nm) in aqueous solutions was found to decrease from ∼50 to −40 mV, and the cellular uptake level by these GNRs in MCF-7 cells decreased with the decrease in zeta potential (Qiu et al, 2010). Positively charged branched polyethyleneimine-decorated GNPs (40, 80 nm) were more likely than negatively charged lipoic acid-GNPs to be endocytosed by HUVECs (Chandran et al, 2017). In monocytes and macrophages, positively charged cysteamine-GNPs (10, 20, and 40 nm) were internalized at a higher level than were negatively charged or zwitterionic GNPs (Oh and Park, 2014).…”

Cellulose Nanocrystals as a Sustainable Raw Material: Cytotoxicity and Applications on Healthcare Technology

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