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Fabrication of corona-free nanoparticles with tunable hydrophobicity.

Moyano DF, Saha K, Prakash G, Yan B, Kong H, Yazdani M, Rotello VM - ACS Nano (2014)

Bottom Line: A protein corona is formed at the surface of nanoparticles in the presence of biological fluids, masking the surface properties of the particle and complicating the relationship between chemical functionality and biological effects.We present here a series of zwitterionic NPs of variable hydrophobicity that do not adsorb proteins at moderate levels of serum protein and do not form hard coronas at physiological serum concentrations.These particles provide platforms to evaluate nanobiological behavior such as cell uptake and hemolysis dictated directly by chemical motifs at the nanoparticle surface.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Massachusetts Amherst , 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.

ABSTRACT
A protein corona is formed at the surface of nanoparticles in the presence of biological fluids, masking the surface properties of the particle and complicating the relationship between chemical functionality and biological effects. We present here a series of zwitterionic NPs of variable hydrophobicity that do not adsorb proteins at moderate levels of serum protein and do not form hard coronas at physiological serum concentrations. These particles provide platforms to evaluate nanobiological behavior such as cell uptake and hemolysis dictated directly by chemical motifs at the nanoparticle surface.

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(a) Cellular uptake (MCF7 cells, 3 h) of zwitterionic NPs ZMe to ZDiPen and NP+ in presence and absence (inset) of serum, showing similar uptake trends for both experimental conditions (24 h result in Figure S21). (b) Hemolytic activity of the NPs at different time points and in the presence and absence of plasma (NPs at a concentration of 500 nM unless otherwise stated).
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fig3: (a) Cellular uptake (MCF7 cells, 3 h) of zwitterionic NPs ZMe to ZDiPen and NP+ in presence and absence (inset) of serum, showing similar uptake trends for both experimental conditions (24 h result in Figure S21). (b) Hemolytic activity of the NPs at different time points and in the presence and absence of plasma (NPs at a concentration of 500 nM unless otherwise stated).

Mentions: Once the absence of corona was established, we investigated the effects of NP hydrophobicity on cellular uptake,43 a phenomenon critically affected by the NP surface and the protein corona.44−46 For this purpose, uptake studies were performed in serum-containing and serum-free media, conditions that critically affect the trend of uptake of NPs of varying hydrophobicity.18 As seen in Figure 3a, there was an increase in cellular uptake with increasing surface hydrophobicity for both cases. In previous studies, when NPs were exposed to the cells in serum-free conditions, increasing hydrophobicity increased cell uptake, similar to the results that we obtained.18 However, when the studies were performed in media with serum, increasing the hydrophobicity of NPs led to greater protein adsorption over the NP surface,47 which in turn reduced the cellular uptake.48,49 In contrast to these prior systems, we obtained similar cellular uptake trends for NPs ZMe–ZDiPen both in the presence and in the absence of serum. This result indicates that direct correlations between the NP surface chemistry and biological responses can be assessed with these NPs, providing further proof of the absence of proteins on the NP surfaces and the direct presentation of the chemical motifs to the cellular environment. As expected, overall uptake was low50 and there was a marked difference in the absolute amount of NP uptake in the presence and absence of serum (∼2-fold higher uptake without serum). This latter phenomenon has been observed previously for other particles independent of their charge,51,52 possibly due to nonspecific binding of proteins and NPs to the cell membrane, a competitive process that slows the uptake of NPs when proteins are present.17,52 This phenomenon may be the rationale behind the fact that the trend of cellular uptake with NP hydrophobicity in serum was more evident at 24 h (Figure S21). Finally, it is important to note that at the conditions of the study the nanoparticles were noncytotoxic (Figure S22).


Fabrication of corona-free nanoparticles with tunable hydrophobicity.

Moyano DF, Saha K, Prakash G, Yan B, Kong H, Yazdani M, Rotello VM - ACS Nano (2014)

(a) Cellular uptake (MCF7 cells, 3 h) of zwitterionic NPs ZMe to ZDiPen and NP+ in presence and absence (inset) of serum, showing similar uptake trends for both experimental conditions (24 h result in Figure S21). (b) Hemolytic activity of the NPs at different time points and in the presence and absence of plasma (NPs at a concentration of 500 nM unless otherwise stated).
© Copyright Policy - editor-choice
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4215884&req=5

fig3: (a) Cellular uptake (MCF7 cells, 3 h) of zwitterionic NPs ZMe to ZDiPen and NP+ in presence and absence (inset) of serum, showing similar uptake trends for both experimental conditions (24 h result in Figure S21). (b) Hemolytic activity of the NPs at different time points and in the presence and absence of plasma (NPs at a concentration of 500 nM unless otherwise stated).
Mentions: Once the absence of corona was established, we investigated the effects of NP hydrophobicity on cellular uptake,43 a phenomenon critically affected by the NP surface and the protein corona.44−46 For this purpose, uptake studies were performed in serum-containing and serum-free media, conditions that critically affect the trend of uptake of NPs of varying hydrophobicity.18 As seen in Figure 3a, there was an increase in cellular uptake with increasing surface hydrophobicity for both cases. In previous studies, when NPs were exposed to the cells in serum-free conditions, increasing hydrophobicity increased cell uptake, similar to the results that we obtained.18 However, when the studies were performed in media with serum, increasing the hydrophobicity of NPs led to greater protein adsorption over the NP surface,47 which in turn reduced the cellular uptake.48,49 In contrast to these prior systems, we obtained similar cellular uptake trends for NPs ZMe–ZDiPen both in the presence and in the absence of serum. This result indicates that direct correlations between the NP surface chemistry and biological responses can be assessed with these NPs, providing further proof of the absence of proteins on the NP surfaces and the direct presentation of the chemical motifs to the cellular environment. As expected, overall uptake was low50 and there was a marked difference in the absolute amount of NP uptake in the presence and absence of serum (∼2-fold higher uptake without serum). This latter phenomenon has been observed previously for other particles independent of their charge,51,52 possibly due to nonspecific binding of proteins and NPs to the cell membrane, a competitive process that slows the uptake of NPs when proteins are present.17,52 This phenomenon may be the rationale behind the fact that the trend of cellular uptake with NP hydrophobicity in serum was more evident at 24 h (Figure S21). Finally, it is important to note that at the conditions of the study the nanoparticles were noncytotoxic (Figure S22).

Bottom Line: A protein corona is formed at the surface of nanoparticles in the presence of biological fluids, masking the surface properties of the particle and complicating the relationship between chemical functionality and biological effects.We present here a series of zwitterionic NPs of variable hydrophobicity that do not adsorb proteins at moderate levels of serum protein and do not form hard coronas at physiological serum concentrations.These particles provide platforms to evaluate nanobiological behavior such as cell uptake and hemolysis dictated directly by chemical motifs at the nanoparticle surface.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Massachusetts Amherst , 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.

ABSTRACT
A protein corona is formed at the surface of nanoparticles in the presence of biological fluids, masking the surface properties of the particle and complicating the relationship between chemical functionality and biological effects. We present here a series of zwitterionic NPs of variable hydrophobicity that do not adsorb proteins at moderate levels of serum protein and do not form hard coronas at physiological serum concentrations. These particles provide platforms to evaluate nanobiological behavior such as cell uptake and hemolysis dictated directly by chemical motifs at the nanoparticle surface.

Show MeSH
Related in: MedlinePlus