Illuminating nano-bio interactions: A spectroscopic perspective

Abstract

IntroductionEngineered nanomaterials (ENMs) provide much-needed breakthroughs for resolving some longstanding challenges in drug delivery and personalized medicine. They exhibit pronounced interactions with biomolecules and the ability to effi ciently cross many physiological barriers due to their small size, which may also cause undesired side effects (also see the Wick et al., Hemmer et al., and Bhattacharya et al. articles in this issue). 1 -5 Spectroscopic tools can be used to determine the underlying biophysical mechanisms and the nature of nanobio interactions at the cellular, subcellular, and protein levels, which cannot be gleaned from traditional toxicological studies. For example, some ENMs release metal ions through dissolution at varying rates in different media, including blood. 6 -11 As discussed in this article, these metal ions can adversely affect the proper functioning of biomolecules and cells through an "action-at-a-distance" mechanism. Spectroscopic tools can clearly identify the net bioavailable metal ion content and help establish relationships between ion-release from ENM and ENM-induced toxicity. As outlined in Figure 1 , this article discusses how various spectroscopic tools (e.g., Raman, photoluminescence, infrared, and surface plasmon) can probe the intrinsic properties of ENMs (e.g., crystallinity and electronic states) and biomolecules (e.g., protein structure) and provide a comprehensive understanding of ENM transport within organisms (e.g., via biodistribution) and new perspectives of biological interactions (e.g., loss of protein structure upon adsorption on ENM) at the nanoscale. Fluorescence imaging of ENM biodistributionThe ultimate prerequisite for a harmful effect from any toxicant is exposure. Therefore, tools allowing the visualization of the nanoparticles (NPs) in vivo are crucial for risk evaluation. On the other hand, the growing utilization of ENMs in potential clinical applications ranging from diagnosis to therapeutic treatment of diseases necessitates a need for understanding their in vivo transport, biodistribution, and long-term fate in the organism. 12 ENMs are known to exhibit a higher uptake by monocytes and macrophages of the mononuclear phagocyte system (a part of the immune system containing phagocytic cells) upon injection into animals, which prevents their rapid clearance through excretion and impairs therapeutic or diagnostic targeting. 2 , 12 Indeed, the clearance mechanisms for most ENMs remain unresolved due to the existing diffi culties in in vivo tracking and monitoring of the ENMs. Fluorescence spectroscopy is one of the important tools in assessing the biological interaction Engineered nanomaterials (ENMs) strongly interact with biomolecules and cells due to their similar size scales. Consequently, ENMs are beginning to emerge as new medical diagnostic tools, probes in cell biology, and delivery vehicles, compelling us to understand the interactions at the nano-bio interface. Optical spectroscopic tools are excellent probes to characterize ENMs...

A hyperspectral and toxicological analysis of protein corona impact on silver nanoparticle properties, intracellular modifications, and macrophage activation

“…[2][3][4][5][6][7] Although concerted efforts from researchers across the globe have led to a better understanding of nanomaterial toxicity, the fundamental mechanisms through which nano-bio interactions occur still remain largely inconclusive. 8 Building on the understanding of adsorbed biomolecules in cellular responses to biomaterials, a new picture of nanotoxicity based on protein-nanomaterial interactions is recently beginning to emerge. [7][8][9][10][11][12] Once placed in a physiological environment, the surface of nanomaterials becomes coated with various biomolecules including proteins, peptides, and lipids, collectively referred to as the "corona".…”

“…8 Building on the understanding of adsorbed biomolecules in cellular responses to biomaterials, a new picture of nanotoxicity based on protein-nanomaterial interactions is recently beginning to emerge. [7][8][9][10][11][12] Once placed in a physiological environment, the surface of nanomaterials becomes coated with various biomolecules including proteins, peptides, and lipids, collectively referred to as the "corona". Previously, others and we have shown that…”

Influence of carbon nanomaterial defects on the formation of protein corona

“…1, 9, 18 Despite this obvious importance of defects and charge transfer in CNM toxicity, the influence of structural and functional defects in CNMs on biomolecular adsorption and immune response remains poorly understood. 21 Although the formation of protein corona on CNMs has been extensively studied in recent years, the underlying physical and chemical processes in protein and defected CNM interactions (e.g., charge transfer between proteins and defects) have not yet been completely understood. To elucidate the role of defects and their associated charge transfer in biological interactions of CNMs, it is imperative to synthesize CNMs with different defect content and study their effects on protein corona.…”

“…19 Indeed, charge transfer interactions between proteins and CNMs have previously been implicated in destabilizing adsorbed proteins/enzymes, which could in turn elicit adverse physiological response. 9,21 While the root cause of ENM (particularly CNM) toxicity is still a subject of ongoing research, numerous studies have identied the presence of bioactive defects in ENMs (including Au, Ag, TiO 2 , SiO 2 , and CNMs) as the common denominator in their physiological response. 1,[12][13][14][15] In case of CNMS, it has been hypothesized that the presence of neutral and charged defects could elicit an adverse physiological response possibly by generating highly reactive oxygen species and inducing structural changes in proteins through charge transfer reactions.…”

The bovine serum albumin protein corona on nanoparticles

“…Conducting a study in real biological fluids is difficult as there are many molecules which compete for binding sites on a nanoparticle surface, and the dynamic nature of the protein corona creates much variability in the precise composition at any time [52]. Furthermore, analyzing which protein or ion is adsorbed to the surface is difficult without trained scientists and expensive techniques [45,103,104]. Thus, a model protein can be used to investigate the nature of the protein corona in a simple aqueous medium to develop an understanding about the overall nature of the protein corona.…”