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. 2014 Oct;10(7):1453-63.
doi: 10.1016/j.nano.2014.01.009. Epub 2014 Feb 7.

Protein corona composition does not accurately predict hematocompatibility of colloidal gold nanoparticles

Marina A Dobrovolskaia  1 , Barry W Neun  2 , Sonny Man  2 , Xiaoying Ye  3 , Matthew Hansen  2 , Anil K Patri  2 , Rachael M Crist  2 , Scott E McNeil  2
Affiliations

Protein corona composition does not accurately predict hematocompatibility of colloidal gold nanoparticles

Marina A Dobrovolskaia et al. Nanomedicine. 2014 Oct.

Abstract

Proteins bound to nanoparticle surfaces are known to affect particle clearance by influencing immune cell uptake and distribution to the organs of the mononuclear phagocytic system. The composition of the protein corona has been described for several types of nanomaterials, but the role of the corona in nanoparticle biocompatibility is not well established. In this study we investigate the role of nanoparticle surface properties (PEGylation) and incubation times on the protein coronas of colloidal gold nanoparticles. While neither incubation time nor PEG molecular weight affected the specific proteins in the protein corona, the total amount of protein binding was governed by the molecular weight of PEG coating. Furthermore, the composition of the protein corona did not correlate with nanoparticle hematocompatibility. Specialized hematological tests should be used to deduce nanoparticle hematotoxicity. From the clinical editor: It is overall unclear how the protein corona associated with colloidal gold nanoparticles may influence hematotoxicity. This study warns that PEGylation itself may be insufficient, because composition of the protein corona does not directly correlate with nanoparticle hematocompatibility. The authors suggest that specialized hematological tests must be used to deduce nanoparticle hematotoxicity.

Keywords: Coagulation; Complement; Hematocompatibility; Nanoparticles; Protein corona.

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Conflict of interest statement

Conflict of Interest: The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

Figures

Figure 1
Figure 1. composition of protein corona over time
30 nm gold colloids were incubated with pooled human plasma for 5 min, 30 min, 1 hr, 6 hr and 24 hr. After several washes with PBS to remove excess plasma, the particle was pelleted and the particle pellet with bound proteins was analyzed by mass spectrometry. Proteins were grouped based on their function. Each bar shows the percentage of bound protein in each category for a given time point.
Figure 2
Figure 2. Kinetics of individual protein binding over time
30 nm colloidal gold nanoparticles were incubated with pooled human plasma and proteins in the corona were identified by mass spectrometry. Presented is the summary of individual proteins identified over 5 min, 30 min, 1 hr, 6 hr and 24 hr incubations.
Figure 3
Figure 3. Kinetics of protein corona over time
30 nm colloidal gold nanoparticles were incubated with pooled human plasma and proteins in the corona were identified by mass spectrometry. The total amount of bound protein identified over 5 min, 30 min, 1 hr, 6 hr and 24 hr time points is shown. The linear trend line is shown as the color-coordinated dashed line, and was used to estimate the general trend in total bound protein between individual time points.
Figure 4
Figure 4. Kinetics of protein binding to gold colloids with various surface coatings
30 nm core colloidal gold nanoparticles uncoated or coated with PEG of various molecular weights (2 kDa, 5 kDa, 10 kDa and 20 kDa) were incubated with pooled human plasma and proteins in the corona were identified by mass spectrometry. Presented is the total amount of bound protein identified over 5 min, 30 min, 1 hr, 6 hr and 24 hr incubation periods.
Figure 5
Figure 5. Nanoparticles and plasma coagulation
(A) 30 nm colloidal gold nanoparticles were studied in vitro to evaluate their pro-coagulant properties. Coagulation in normal control (N), abnormal control (ABN) and untreated healthy donor plasma (UT) was initiated by the addition of Neoplastin reagent. Water (H2O) and gold colloids (30 nm Au-NP) were also tested for initiation of coagulation in samples of untreated healthy donor plasma. (B) Pooled human plasma was either untreated (UT) or treated with 30 nm gold colloids (Au-NP), high concentration (0.15NIHU/mL) of thrombin (thrombin D1) or low (0.015NIH U/mL) concentration of thrombin (thrombin D10) for 30 min at 37°C. Plasma coagulation was initiated in all samples by the addition of Neoplastin reagent (PT) or PTTa reagent and calcium chloride (APPT); >360 refers to the absence of detectable coagulation within 6 min; each bar shows the mean of duplicate results (%CV < 5).
Figure 6
Figure 6. Nanoparticles and complement activation
(A) 30 nm colloidal gold nanoparticles were studied in vitro to evaluate their ability to activate the human complement system. Pooled normal human plasma was treated with PBS, cobra venom factor (CVF) or nanoparticles for 30 min at 37°C, and complement split products iC3b, C4d and Bb were measured by ELISA. (B) Pooled human plasma was treated with 30 nm gold colloids (30 nm Au-NP) or vehicle (water) for 30 min at 37°C. Following incubation, plasma was spun down to remove particles, and supernatants were treated with PBS, CVF or Taxol. Complement split products were monitored by ELISA. Each bar shows the mean ± SD (N=3).
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