The concept of bio-corona in modulating the toxicity of engineered nanomaterials (ENM)

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Highlights

  • “Nanotoxicology” has emerged an autonomous field with an explosive growth.

  • Nanomaterials adsorb (bio)molecules forming the so-called (bio)molecule corona.

  • (Fine-)tune of the corona composition could enable new possibilities in nanomedicine.

Abstract

Besides the wide use of engineered nanomaterials (ENM) in technical products, their application spectrum in biotechnology and biomedicine is steadily increasing. In complex physiological environments the physico-chemical properties and the behavior of nanoparticles (NPs) are challenging to characterize. Biomolecules rapidly adsorb to the nanomaterial, leading to the formation of the protein/biomolecule corona, which critically affects the nanomaterials' (patho)biological and technical identities. This formation can trigger an immune response and affect nanoparticles' toxicity and targeting capabilities. In this review, we provide a survey of recent findings on the (protein)corona-nanoparticle interaction and discuss how the corona modulates both cytotoxicity and the immune response as well as to improve the efficacy of targeted delivery of nanocarriers.

Introduction

Since 2004 “nanotoxicology” has emerged an autonomous field with an explosive growth. As illustrated in Fig. 1, querying the PubMed database with the search term ‘nanotoxicology’ reveals that more than 238 reports have been published on this topic by September 2015 (in 2004 only two reports were found). Such developments are influenced by the increasing exposure of humans and the environment to nanomaterials (NM). The ability to create nanomaterial in a wide variety of different combinations concerning their chemistry, shape, size and surface properties led to the concentration of the nanotoxicological aspects regarding these NM characteristics. Although, due to their high surface energy, NMs adsorb (bio)molecules upon contact with any kind of biological environment, consequently forming the so-called (bio)molecule corona, the role of this corona in toxicological aspects has been completely neglected so far (Docter, D., et al., 2015a, Nel, A.E., et al., 2009). As the topic of this mini-review is about the “the concept of the bio-corona”, we again inquired the PubMed database with the search terms ‘nanotoxicology’ AND ‘corona’. From 2004 to 2007 we found zero reports and by September 2015 only 14 studies were published on this topic (Fig. 1). In this mini-review we will introduce you to the history and the importance of the biomolecule corona, on its impact on biomedical applications as well as its influence on the still young field of nanotoxicology.

Section snippets

The corona concept

The applications of engineered nanomaterials (ENMs) are not only increasing in technical products but also more and more in biotechnology and biomedicine (Docter, D., et al., 2015a, Reese, M., 2013, Webster, T.J., 2013, Docter, D., et al., 2015b, Setyawati, M.I., et al., 2015). Thus, the ‘marriage’ of nanotechnology with biomedicine defines one of the most exciting and cross-disciplinary developments over the last decade (Reese, M., 2013, Webster, T.J., 2013). Nanomedicine is the field of

Targeting the capability of nanoparticles in the light of the biomolecule corona

Over the past decades nanocarriers were designed in the attempt to: i) increase drug bioavailability and avoid drug inactivation, which is particularly important in the case of poorly soluble compounds, or degradation by blood proteases/peptidases or nucleases (Riehemann et al., 2009); ii) minimize side effects due to a non-specific body distribution of the drug and to the high amount of drug commonly used (Ferrari, 2005), and iii) selectively deliver the payload to the affected area, thereby

Application routes and biodistribution of nanoparticles

Upon administration NPs will interact with cells. It is well accepted from cell-culture studies that almost all mammalian cells are, in principle, capable to incorporate NPs to some extent, due to a variety of unspecific uptake mechanisms (Hillaireu and Couvreur, 2009). Many studies have explored the NP properties which influence efficiency of cellular uptake and determine also their intracellular processing resulting in complete or partly degradation, or storage of NPs in unchanged form in the

Toxicological implication of the protein corona

The formation of a protein corona impacts not only on the delivery properties of NPs (e.g. biodistribution and clearance), it can also influence their toxicity and pathophysiology (Tenzer et al., 2013). Studies on the specific role of the biomolecule corona in favoring toxicity have produced contrasting results. For example, in the study by Tenzer et al., the authors showed the (patho)biological relevance of the protein corona in in vitro studies of primary human cell models of the blood

Conclusion

A major challenge in nanomedicine is to engineer NPs which are able to overcome the biological barriers that separate them from the target cells. To reach its target, synthetic NPs get into contact with a biological environment that confers part of its ‘bio’ nature on them, thereby endowing them with a bio-identity. The ability to (fine-)tune the protein corona composition itself could potentially enable new possibilities in overcoming biological barriers, such as the blood–brain-barrier, help

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Acknowledgments

Grant support: BMBF-MRCyte (13N1202)/NanoBEL (03XP0003H)/DENANA (03X0152H), Zeiss-ChemBioMed (0563-2.8/399/1), Stiftung Rheinland-Pfalz (NanoScreen), DFGSPP1313, PTE-foundation and Fonds der chemischen Industrie. We apologize to all colleagues whose work could not be cited due to space limitations. We thank Dr. Christian Eufinger and the PhD L&L group for helpful discussion.

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