Large scale molecular simulations of nanotoxicity

Abstract

The widespread use of nanomaterials in biomedical applications has been accompanied by an increasing interest in understanding their interactions with tissues, cells, and biomolecules, and in particular, on how they might affect the integrity of cell membranes and proteins. In this mini-review, we present a summary of some of the recent studies on this important subject, especially from the point of view of large scale molecular simulations. The carbon-based nanomaterials and noble metal nanoparticles are the main focus, with additional discussions on quantum dots and other nanoparticles as well. The driving forces for adsorption of fullerenes, carbon nanotubes, and graphene nanosheets onto proteins or cell membranes are found to be mainly hydrophobic interactions and the so-called π-π stacking (between aromatic rings), while for the noble metal nanoparticles the long-range electrostatic interactions play a bigger role. More interestingly, there are also growing evidences showing that nanotoxicity can have implications in de novo design of nanomedicine. For example, the endohedral metallofullerenol Gd@C₈₂(OH)₂₂ is shown to inhibit tumor growth and metastasis by inhibiting enzyme MMP-9, and graphene is illustrated to disrupt bacteria cell membranes by insertion/cutting as well as destructive extraction of lipid molecules. These recent findings have provided a better understanding of nanotoxicity at the molecular level and also suggested therapeutic potential by using the cytotoxicity of nanoparticles against cancer or bacteria cells.

Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems

“…514–516 However, in de novo biomedical applications, the cytotoxicity of nanomaterials can also be considered as a therapeutic potential and can be utilized in the killing of cancer cells, and the eradication of bacterial cells, etc. 517 …”

Towards understanding of nanoparticle–protein corona

“…With the increasing applications of nanomaterials in practice, there are growing concerns on their potential biosafety (Ge et al 2008(Ge et al , 2011a(Ge et al , b, 2012aJimenez-Cruz et al 2014;Laurent et al 2013b;Mortensen et al 2013;Pan et al 2012;Rivera-Gil et al 2012;Zhao et al 2008;Zhou and Gao 2014;Zhu et al 2015;Zuo et al 2013). When exposed to biofluids, the surface of nanoparticles is immediately adsorbed by the suspending proteins forming the corresponding complexes of the so-called nanoparticle-protein corona, which endow the nanoparticles with new biological identities (Fleischer and Payne 2014a;Lundqvist 2013;Mirshafiee et al 2013;Monopoli et al 2012).…”

Silk Fibroin–Substrate Interactions at Heterogeneous Nanocomposite Interfaces

“…In the case of interactions of peptides with graphitic surfaces, MD simulations have shown that van der Waals interactions play a dominant role in the adsorption process . There is an overall agreement that hydrophobic interactions and π–π stacking also serve as driving forces for adsorption of peptides and proteins on graphene . Thus, the presence of graphene affects peptides conformations and reduces secondary structure stability as compared to the structure in solution .…”