Blood protein and blood cell interactions with gold nanoparticles: the need for in vivo studies

Abstract

Gold nanoparticles (GNPs) have gained in prominence within the field of nanomedicine with recent advancement of several embodiments to clinical trials. To ensure their success in the clinic it has become increasingly clear that a deeper understanding of the biological interactions of GNPs is imperative. Since the majority of GNPs are intended for systemic intravenous use, an immediate and critical biological interaction is between the blood and the GNP. Blood is composed of plasma proteins and cells. Both of these components can induce downstream effects upon interacting with GNPs that ultimately influence their medical impact. For instance, proteins from the blood can cover the GNP to create a biological identity through formation of a protein corona that is quite different from the originally synthesized GNP. Once in the bloodstream this protein coated GNP evokes both positive and negative physiological responses such as biodistribution into tissue for therapy (i.e., cancer) and toxicity or off target accumulation in the reticuloendothelial system (RES) that must be controlled for optimal use. In this review, we summarize predominantly in vitro studies of GNP interactions with blood plasma proteins and blood cells and make the case that more in vivo study is urgently needed to optimal design and control GNP use in medicine. In some cases where no specific GNP blood studies exist, we draw the readers ' attention to studies conducted with other types of nanoparticles as reference.

Adsorption Induced Changes of Human Hemoglobin on Ferric Pyrophosphate Nanoparticle Surface Probed by Isotope Exchange Mass Spectrometry: An Implication on Structure–Function Correlation

“…However, NPs that escapes from the natural mechanism of excretion, gets retained in cells and tissues resulting in NP-induced toxicity . Furthermore, NPs that are administered through intravenous delivery enter the vascular system, thereby interacting with the blood proteins and blood cells . Proteins in the blood adsorb on the surface of NPs (opsonization) facilitating the process of phagocytosis through monocytes and macrophages resulting in its elimination from the circulatory system. , However, erythrocytes, which make up 96% of the blood cells are devoid of phagocytic machinery.…”

The Hemocompatibility of Nanoparticles: A Review of Cell–Nanoparticle Interactions and Hemostasis

“…Another cellular constituent of blood, which is often overlooked in terms of contribution to hemostasis, is represented by leukocytes. These cells are subdivided into monocytes, granulocytes and lymphocytes (Table 2) and play a critical role in inflammation, immunity and host defense systems [66]. However, recent studies have also found that these cells actively contribute to normal hemostasis as well as thrombotic conditions [67].…”

“…Another important observation is that a positive charge on the surface of NPs can, in addition to warranting effective cellular drug delivery, also ensue immunotoxicity through the stimulation of inflammatory immune responses. Several researchers have found that cationic liposomes can stimulate neutrophils and induce oxidative bursts in these cells [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,...…”

Gold Nanoparticle Quantification With Total Reflection X-ray Fluoresence

“…Within minutes of the intravenous injection of AuNPs, erythrocytes, monocytes, macrophages, neutrophils, and dendritic cells recognize the AuNPcorona complexes, phagocytosing nearly 95% of the injected dose. This leads to the eventual destruction and removal of the AuNPs from the blood stream without ever reaching the tumor [226]. Considering these barriers, maximizing the delivery of AuNPs in solid tumors must undoubtedly involve the study of interactions with blood.…”