Effect of Nanoparticle Surface Charge at the Plasma Membrane and Beyond

Arvizo, Rochelle R.; Miranda, Oscar R.; Thompson, Michael Andrew; Pabelick, Christina M.; Bhattacharya, Resham; Robertson, John; Rotello, Vincent M.; Prakash, Y. S.; Mukherjee, Priyabrata

doi:10.1021/nl101140t

Cited by 563 publications

(475 citation statements)

References 26 publications

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“…A similar effect has been reported for other cationic NPs, 43,44 and in silico analyses of the process 45,46 explain it by NP entry through nanosized holes in the plasma membrane usually connected to significant cytotoxicity.…”

Section: ■ Results and Discussionsupporting

confidence: 78%

Fluorinated and Charged Hydrogenated Alkanethiolates Grafted on Gold: Expanding the Diversity of Mixed-Monolayer Nanoparticles for Biological Applications

et al. 2016

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Low intrinsic toxicity, high solubility, and stability are important and necessary features of gold nanoparticles to be used in the biomedical field. In this context, charged nanoparticles proved to be very versatile, and among them charged mixed-monolayer gold nanoparticles, displaying monolayers with well-defined morphologies, represent a paradigm. By using mixtures of hydrogenated and fluorinated thiols, the formation of monolayer domains may be brought to an extreme because of the immiscibility of fluorinated and hydrogenated chains. Following this rationale, mixed monolayer gold nanoparticles featuring ammonium, sulfonate, or carboxylic groups on their surface were prepared by using amphiphilic hydrogenated thiols and 1H,1H,2H,2H-perfluoro-alkanethiols. The toxicity of these systems was assessed in HeLa cells and was found to be, in general, low even for the cationic nanoparticles which usually show a high cytotoxicity and is comparable to that of homoligand gold nanoparticles displaying amphiphiliccharge neutralhydrogenated or fluorinated thiolates in their monolayer. These properties make the mixed ligand monolayer gold nanoparticles an interesting new candidate for medical application.

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Section: ■ Results and Discussionsupporting

confidence: 78%

Fluorinated and Charged Hydrogenated Alkanethiolates Grafted on Gold: Expanding the Diversity of Mixed-Monolayer Nanoparticles for Biological Applications

et al. 2016

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“…We observed that positively charged nanoparticles had the highest cytotoxicity which is consistent with previous reports [19,22], whereas negatively charged nanoparticles induced only marginal cell death. Thus, whilst nanoparticles potentially change the conformation of the cell membrane, resulting in a disruption of cellular processes and membrane integrity [23,24], most interactions with the cell membrane do not cause any membrane disruption or extraction of the protein from the plasmalemma, as previously observed in the case of cyclodextrins [25].…”

Section: Discussionsupporting

confidence: 92%

“…Recently, Arvizo et al [19] reported that gold nanoparticles, depending on their surface charge, caused changes in membrane potential. Nevertheless, P-gp function has repeatedly been observed to be independent of membrane potential [20].…”

Section: Discussionmentioning

confidence: 99%

Nanoparticles attenuate P-glycoprotein/MDR1 function in A549 human alveolar epithelial cells

Salomon

Ehrhardt

2011

European Journal of Pharmaceutics and Biopharmaceutics

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P-glycoprotein/MDR1 (P-gp) is a well characterised membrane transporter relevant in drug disposition and multi-drug resistance. In this study, we aimed to investigate in how far nanoparticulates impair the function of the P-gp transport system, and which particle properties govern these interactions.Expression and function of P-gp was confirmed in A549 cell monolayers. Rhodamine 123 (Rh123) release studies were carried out in the presence of known inhibitors of Pgp function (i.e., cyclosporine A and verapamil), under ATP depletion (NaN 3 /DOG) and after acute exposure to nanoparticles (NPs) with different surface modifications, ζ-potentials and sizes (plain, carboxylated, and amine-and sulphate-modified). The cytotoxic potential of NPs on A549 monolayers was evaluated by MTT assay. The effects on P-gp protein level, after incubation with NPs, were investigated by Western blot analysis of A549 cell lysate and supernatant. Cellular retention of Rh123 was significantly (P < 0.05) increased in the presence of carboxylated (100 nm), amine-and sulphate-modified NPs. A slight, but not significant, decrease in Rh123 release was also observed for plain latex and carboxylated (500 nm)NPs. The MTT assay demonstrated that most NPs caused only marginal levels of cytotoxicity (78-88% cell viability); the positively charged amine-NPs, however, were considerably more cytotoxic. Western blot showed that NPs did not cause any cell membrane disruption.Our findings suggest that nanomaterials can attenuate membrane transporter function depending on their size and surface properties and hence, might influence disposition of xenobiotics as well as endogenous substrates.

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“…Samples were analyzed by INAA as previously described (49), and details are provided in SI Materials and Methods.…”

mentioning

confidence: 99%

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Arvizo¹,

Saha²,

Wang³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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217

215

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Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the proliferation of cancer cells in a size-and concentration-dependent manner by abrogating MAPK-signaling. In addition, these AuNPs reverse epithelial-mesenchymal transition (EMT) in cancer cells by reducing secretion of a number of proteins involved in EMT, up-regulating E-Cadherin, and down-regulating Snail, N-Cadherin, and Vimentin. Inhibition of MAPK signaling and reversal of EMT upon AuNP treatment inhibits tumor growth and metastasis in two separate orthotopic models of ovarian cancer. Western blot analyses of tumor tissues reveal up-regulation of E-Cadherin and down-regulation of Snail and phospho-MAPK, confirming the reversal of EMT and inhibition of MAPK signaling upon AuNP treatment. The ability of a single selftherapeutic nanoparticle to abrogate signaling cascades of multiple growth factors is distinctive and purports possible medical applications as potential antitumor and antimetastatic agent.drug delivery | heparin-binding growth factors

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Effect of Nanoparticle Surface Charge at the Plasma Membrane and Beyond

Cited by 563 publications

References 26 publications

Fluorinated and Charged Hydrogenated Alkanethiolates Grafted on Gold: Expanding the Diversity of Mixed-Monolayer Nanoparticles for Biological Applications

Fluorinated and Charged Hydrogenated Alkanethiolates Grafted on Gold: Expanding the Diversity of Mixed-Monolayer Nanoparticles for Biological Applications

Nanoparticles attenuate P-glycoprotein/MDR1 function in A549 human alveolar epithelial cells

Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

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