Identification of physicochemical properties that modulate nanoparticle aggregation in blood

Abstract

Inorganic materials are receiving significant interest in medicine given their usefulness for therapeutic applications such as targeted drug delivery, active pharmaceutical carriers and medical imaging. However, poor knowledge of the side effects related to their use is an obstacle to clinical translation. For the development of molecular drugs, the concept of safe-by-design has become an efficient pharmaceutical strategy with the aim of reducing costs, which can also accelerate the translation into the market. In the case of materials, the application these approaches is hampered by poor knowledge of how the physical and chemical properties of the material trigger the biological response. Hemocompatibility is a crucial aspect to take into consideration for those materials that are intended for medical applications. The formation of nanoparticle agglomerates can cause severe side effects that may induce occlusion of blood vessels and thrombotic events. Additionally, nanoparticles can interfere with the coagulation cascade causing both pro- and anti-coagulant properties. There is contrasting evidence on how the physicochemical properties of the material modulate these effects. In this work, we developed two sets of tailored carbon and silica nanoparticles with three different diameters in the 100–500 nm range with the purpose of investigating the role of surface curvature and chemistry on platelet aggregation, activation and adhesion. Substantial differences were found in the composition of the protein corona depending on the chemical nature of the nanoparticles, while the surface curvature was found to play a minor role. On the other hand, large carbon nanoparticles (but not small carbon nanoparticles or silica nanoparticles) have a clear tendency to form aggregates both in plasma and blood. This effect was observed both in the presence or absence of platelets and was independent of platelet activation. Overall, the results presented herein suggest the existence of independent modes of action that are differently affected by the physicochemical properties of the materials, potentially leading to vessel occlusion and/or formation of thrombi in vivo.

Efficacy, Biocompatibility and Degradability of Carbon Nanoparticles for Photothermal Therapy of Lung Cancer

“…Although a decrease of ζ-potential was detected, as a consequence of the formation of a protein corona, no substantial agglomeration was observed, likely because of a stabilizing effect of adsorbed serum proteins by steric hindrance. This effect was similar to our previous observations in human plasma and blood [23]. Taken together, these results suggest that CNPs possess several desirable properties, including colloidal stability in relevant media.…”

“…These CNPs were shown to be noncytotoxic toward a murine macrophage cell line and significant antioxidant activity was observed, as a consequence of their ability to scavenge hydroxyl radicals. Finally, in a subsequent study CNPs were shown to remain stable in human plasma and blood, implying good hematocompatibility [23].…”

Risk Management Framework for Nano-Biomaterials Used in Medical Devices and Advanced Therapy Medicinal Products

“…However, at several levels there is high complexity associated with the hazard assessment of NBM, both for human risks as well as for the environment [ 21 , 22 ]. Common issues are dealing with the physicochemical identity of the NBMs, the existence of different nanoforms and their transformations in physiological and environmental media (e.g., biocorona formation, weathering/ageing) [ 23 , 24 , 25 ]. In addition, it can be questioned which are the most relevant biomarkers for NBM hazard testing and whether they are currently adequately addressed in the Organisation for Economic Co-operation and Development (OECD) guidelines used for regulatory purposes.…”

Ethyl Hydroxyethyl Cellulose—A Biocompatible Polymer Carrier in Blood

“…The interference of nanomaterials with platelets and the resulting enhancement of platelet aggregation behavior may strongly hamper their use in therapeutic applications, blood analytics, and diagnostics [ 15 ]. The use of nanomaterials as carriers in the bloodstream requires that these materials minimally interfere with the clotting system.…”