Disease-related metabolites affect protein–nanoparticle interactions

Abstract

Once in biological fluids, the surface of nanoparticles (NPs) is rapidly covered with a layer of biomolecules (i.e., the "protein corona") whose composition strongly determines their biological identity, regulates interactions with biological entities including cells and the immune system, and consequently directs the biological fate and pharmacokinetics of nanoparticles. We recently introduced the concept of a "personalized protein corona" which refers to the formation of different biological identities of the exact same type of NP after being exposed to extract plasmas from individuals who have various types of diseases. As different diseases have distinct metabolomic profiles and metabolites can interact with proteins, it is legitimate to hypothesize that metabolomic profiles in plasma may have the capacity to, at least partially, drive the formation of a personalized protein corona. To test this hypothesis, we employed a multi-scale approach composed of coarse-grained (CG) and all atom (AA) molecular dynamics (MD) simulations to probe the role of glucose and cholesterol (model metabolites in diabetes and hypercholesterolemia patients) in the interaction of fibrinogen protein and polystyrene NPs. Our results revealed that glucose and cholesterol had the capacity to induce substantial changes in the binding site of fibrinogen to the surface of NPs. More specifically, the simulation results demonstrated that increasing the metabolite amount could change the profiles of fibrinogen adsorption and replacement, what is known as the Vroman effect, on the NP surface. In addition, we also found out that metabolites can substantially determine the immune triggering potency of the fibrinogen-NP complex. Our proof-of-concept outcomes further emphasize the need for the development of patient-specific NPs in a disease type-specific manner for high yielding and safe clinical applications.

The Complexity of the Homeopathic Healing Response Part 1: The Role of the Body as a Complex Adaptive System in Simillimum-Initiated Recovery from Disease

“…102 This also means adopting research technologies and analytical methods that can objectively document existence of and changes in the complexity of non-linear modulation of patient physiology: for example, in sleep and waking EEG 17 and/or heart rate variability and/or spectroscopy of blood patterns in health and disease. 103,104…”

The Complexity of the Homeopathic Healing Response Part 2: The Role of the Homeopathic Simillimum as a Complex System in Initiating Recovery from Disease

“…135,136,141,143 Disease-related metabolomics play a role in how blood plasma proteins interact with exogenous nanoparticles. 136 Smaller nanoparticle sizes, which occur at greater concentrations in higher versus lower potencies, 36,92 are known to modulate the formation, composition, and properties of the protein corona that becomes the nanoparticle coat. 17,18,134 In vivo, higher versus lower homeopathic potencies exert longer durations of action.…”

“…151 Separately, mainstream nano-medicine researchers are already beginning to consider the therapeutic potential of different personalized protein corona coatings on quantitatively higher dose nano-structures. 135,136,143 For most clinical scenarios, however, the simillimum for the patient's current state would still be the single correctly chosen homeopathic medicine whose information resonates with and literally adsorbs onto its surface the most relevant pattern of endogenous proteins reflecting the patient's current state: that is, the biological information pattern of the recipient individual in the protein corona. 152 The clinically claimed need in homeopathy for even more precise symptom pattern matching to choose the correct homeopathic medicine at higher versus lower potencies may derive in part from differences in potency-related nanoparticle sizes and consequently the resultant protein corona patterns that form.…”

Effects of Nanoparticle Electrostatics and Protein–Protein Interactions on Corona Formation: Conformation and Hydrodynamics

“…To overcome this, Shao and Hall, and Wang et al recently performed all‐atom simulations, showing the conformational change of SA protein adsorbed on gold nanoparticles. Tavakol et al's all‐atom and CG simulations showed the effects of glucose and cholesterol on the adsorption of plasma proteins onto PS particles . However, the effects of protein–protein interactions on the conformation and dynamics of proteins of inner and outer protein layers have not yet been systematically studied through all‐atom simulations.…”

“…Tavakol et al's all-atom and CG simulations showed the effects of glucose and cholesterol on the adsorption of plasma proteins onto PS particles. [47] However, the effects of protein-protein interactions on the conformation and dynamics of proteins of inner and outer protein layers have not yet been systematically studied through all-atom simulations.…”