Modeling the Time Evolution of the Nanoparticle-Protein Corona in a Body Fluid

Background: Nanoparticles in contact with biological fluids interact with proteins and other biomolecules, thus forming a dynamic corona whose composition varies over time due to continuous protein association and dissociation events. Eventually equilibrium is reached, at which point the continued exchange will not affect the composition of the corona. Results: We developed a simple and effective dynamic model of the nanoparticle protein corona in a body fluid, namely human plasma. The model predicts the time evolution and equilibrium composition of the corona based on affinities, stoichiometries and rate constants. An application to the interaction of human serum albumin, high density lipoprotein (HDL) and fibrinogen with 70 nm N-iso-propylacrylamide/N-tert-butylacrylamide copolymer nanoparticles is presented, including novel experimental data for HDL. Conclusions: The simple model presented here can easily be modified to mimic the interaction of the nanoparticle protein corona with a novel biological fluid or compartment once new data will be available, thus opening novel applications in nanotoxicity and nanomedicine

Clinical evaluation of plasma high-density lipoprotein subfractions (HDL2, HDL3) in non-insulin-dependent diabetics with coronary artery disease

statement of the problem: Low levels of high-density lipoprotein cholesterol (HDL-C) have a strong association with coronary artery disease (CAD) in patients with non-insulin-dependent diabetes mellitus (NIDDM). In this study, we tried to evaluate whether one or both of the major HDL subclasses (HDL2, HDL3) is strongly associated with the risk of CAD in NIDDM subjects. Methods: The separation of HDL subclasses was carried out by ultracentrifugation in a Beckman Airfuge. HDL2 subclass was isolated from the supernatant and its cholesterol content was measured enzymatically. Plasma HDL3 cholesterol was calculated as the difference between results for total HDL cholesterol and HDL2 cholesterol. Results: NIDDM patients with CAD had significantly higher triglyceride levels compared to either control (217.09 +/- 55.04 versus 89.62 +/- 31.29 mg/dl, P=.001) or CAD patients without NIDDM (217.09 +/- 55.04 versus 156.28 +/- 46.39 mg/dl, P<.05). However, in the diabetic patients with CAD, there was a statistically significant decrease in HDL cholesterol (39.63<plus/minus>8.59 versus 55.86 +/- 13.49 mg/dl, P<.01), HDL2 cholesterol (8.74<plus/minus>3.28 versus 16.95 +/-5.73 mg/dl, P<.001),and HDL3 cholesterol (31.23<plus/minus>7.41 versus 38.91 +/-8.93 mg/dl, P<.05) in comparison to nondiabetic controls. Moreover, in the comparison between non-insulin-dependent diabetics with CAD and CAD subjects without NIDDM, HDL cholesterol (39.63<plus/minus>8.59 versus 46.13 +/-6.33 mg/dl, P<.05) and HDL2 cholesterol (8.74<plus/minus>3.28 versus 11.84 +/-4.01 mg/dl, P<.02) were significantly reduced, while HDL3 cholesterol levels were (31.23<plus/minus>7.41 versus 34.29 +/-7.94 mg/dl, P=.92) unaltered. Additionally, the percentage reduction of cholesterol in HDL2 fraction was proportionately greater than the decrease in HDL3 subclass in both comparisons. Moreover, in NIDDM with CAD, HDL cholesterol was reduced by 29% and 14%, HDL2 cholesterol by 48% and 26%, and HDL3 cholesterol by 20% and 9%, compared relatively to controls and CAD subjects without NIDDM. Conclusions: In conclusion, HDL2 is the more variable subclass and reflects changes in HDL. This suggests that the protective role of total I IDL against CAD is mainly mediated through HDL2 fraction. Therefore, HDL2 might be a better predictor of coronary heart disease than total I-IDL, in non-insulin-dependent diabetes mellitus. (C) 2001 Elsevier Science Inc. All rights reserved