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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) Particle size distribution for cationic NP+ and zwitterionic particle ZMe in the presence and absence of serum proteins (1% serum, background) evidencing the formation of NP/protein complexes (∼20 nm) with NP+ but not with ZMe (complete spectra and additional analysis in plasma in Supporting Information). (b) Lack of corona formation for zwitterionic particles in serum and corona formation for TEG (lacking zwitterionic headgroup) and anionic NP–. (c) Comparison between the experimental DLS profiles of each NP in serum with the additive histogram of the combination of the individual serum and NP. (d) Residuals of the spectra in serum after removing the individual NP and serum histograms, evidencing corona and aggregate formation for NP+ with minimal residual observed for ZMe (additional NPs in Figure S14). (e) Dilution studies showing lack of hard corona formation for ZMe after incubation in 55% human serum, with contrasting behavior by the cationic NP+ particle. (f) Sedimentation experiments for the series of NPs in 55% plasma showing that zwitterionic NPs ZMe to ZDiPen did not aggregate, in contrast to NP+, NP–, and TEG that formed pellets.
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fig2: (a) Particle size distribution for cationic NP+ and zwitterionic particle ZMe in the presence and absence of serum proteins (1% serum, background) evidencing the formation of NP/protein complexes (∼20 nm) with NP+ but not with ZMe (complete spectra and additional analysis in plasma in Supporting Information). (b) Lack of corona formation for zwitterionic particles in serum and corona formation for TEG (lacking zwitterionic headgroup) and anionic NP–. (c) Comparison between the experimental DLS profiles of each NP in serum with the additive histogram of the combination of the individual serum and NP. (d) Residuals of the spectra in serum after removing the individual NP and serum histograms, evidencing corona and aggregate formation for NP+ with minimal residual observed for ZMe (additional NPs in Figure S14). (e) Dilution studies showing lack of hard corona formation for ZMe after incubation in 55% human serum, with contrasting behavior by the cationic NP+ particle. (f) Sedimentation experiments for the series of NPs in 55% plasma showing that zwitterionic NPs ZMe to ZDiPen did not aggregate, in contrast to NP+, NP–, and TEG that formed pellets.

Mentions: To determine the preliminary interactions of the synthesized NPs with proteins,26,39 dynamic light scattering (DLS) measurements were recorded in the presence of 1% serum, the highest concentration that did not overwhelm the NP signal (Figure S13; experiment also performed in 1% plasma, Figure S15). The principal change in the DLS profile of serum after the addition of NP+ (cationic), NP– (anionic), and TEG (neutral oligo(ethylene glycol)-capped particles) was the shift of the ∼9 nm hydrodynamic diameter (dh) peak to ∼20 nm, evidencing the formation of discrete protein–NP complexes, namely, the protein corona (Figure 2a,b). For NP+, the formation of a peak above 1000 nm was also observed, indicating the presence of extended protein–NP aggregates (Figure S13). In contrast, only the peak at ∼9 nm was observed with the zwitterionic NPs ZMe to ZDiPen (Figure 2a,b). These results can easily be contrasted by comparing the predicted histogram in the case where no corona is formed (the addition of the individual serum and NP histograms) with the experimental DLS distribution after mixing the NPs with serum (Figure 2c). As observed in Figure 2d, the subtraction of the experimental histograms from the predicted additive histograms shows that while NP+ presents residuals at the ∼20 and ∼1000 nm zones indicative of both aggregation and corona formation, ZMe has minimal residual, indicating the absence of corona at these protein levels (additional NPs in Figures S14 and S16).


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) Particle size distribution for cationic NP+ and zwitterionic particle ZMe in the presence and absence of serum proteins (1% serum, background) evidencing the formation of NP/protein complexes (∼20 nm) with NP+ but not with ZMe (complete spectra and additional analysis in plasma in Supporting Information). (b) Lack of corona formation for zwitterionic particles in serum and corona formation for TEG (lacking zwitterionic headgroup) and anionic NP–. (c) Comparison between the experimental DLS profiles of each NP in serum with the additive histogram of the combination of the individual serum and NP. (d) Residuals of the spectra in serum after removing the individual NP and serum histograms, evidencing corona and aggregate formation for NP+ with minimal residual observed for ZMe (additional NPs in Figure S14). (e) Dilution studies showing lack of hard corona formation for ZMe after incubation in 55% human serum, with contrasting behavior by the cationic NP+ particle. (f) Sedimentation experiments for the series of NPs in 55% plasma showing that zwitterionic NPs ZMe to ZDiPen did not aggregate, in contrast to NP+, NP–, and TEG that formed pellets.
© Copyright Policy - editor-choice
Related In: Results  -  Collection

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

fig2: (a) Particle size distribution for cationic NP+ and zwitterionic particle ZMe in the presence and absence of serum proteins (1% serum, background) evidencing the formation of NP/protein complexes (∼20 nm) with NP+ but not with ZMe (complete spectra and additional analysis in plasma in Supporting Information). (b) Lack of corona formation for zwitterionic particles in serum and corona formation for TEG (lacking zwitterionic headgroup) and anionic NP–. (c) Comparison between the experimental DLS profiles of each NP in serum with the additive histogram of the combination of the individual serum and NP. (d) Residuals of the spectra in serum after removing the individual NP and serum histograms, evidencing corona and aggregate formation for NP+ with minimal residual observed for ZMe (additional NPs in Figure S14). (e) Dilution studies showing lack of hard corona formation for ZMe after incubation in 55% human serum, with contrasting behavior by the cationic NP+ particle. (f) Sedimentation experiments for the series of NPs in 55% plasma showing that zwitterionic NPs ZMe to ZDiPen did not aggregate, in contrast to NP+, NP–, and TEG that formed pellets.
Mentions: To determine the preliminary interactions of the synthesized NPs with proteins,26,39 dynamic light scattering (DLS) measurements were recorded in the presence of 1% serum, the highest concentration that did not overwhelm the NP signal (Figure S13; experiment also performed in 1% plasma, Figure S15). The principal change in the DLS profile of serum after the addition of NP+ (cationic), NP– (anionic), and TEG (neutral oligo(ethylene glycol)-capped particles) was the shift of the ∼9 nm hydrodynamic diameter (dh) peak to ∼20 nm, evidencing the formation of discrete protein–NP complexes, namely, the protein corona (Figure 2a,b). For NP+, the formation of a peak above 1000 nm was also observed, indicating the presence of extended protein–NP aggregates (Figure S13). In contrast, only the peak at ∼9 nm was observed with the zwitterionic NPs ZMe to ZDiPen (Figure 2a,b). These results can easily be contrasted by comparing the predicted histogram in the case where no corona is formed (the addition of the individual serum and NP histograms) with the experimental DLS distribution after mixing the NPs with serum (Figure 2c). As observed in Figure 2d, the subtraction of the experimental histograms from the predicted additive histograms shows that while NP+ presents residuals at the ∼20 and ∼1000 nm zones indicative of both aggregation and corona formation, ZMe has minimal residual, indicating the absence of corona at these protein levels (additional NPs in Figures S14 and S16).

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