Corona protein composition and cytotoxicity evaluation of ultra-small zeolites synthesized from template free precursor suspensions

Abstract

The toxicity of two types of ultra-small zeolites (8-18 nm) with LTL-and EMT-type structures is reported.Both the LTL-and EMT-type zeolites belong to the same group of molecular sieves; they have large pores (7.1-7.5 Å) and low silica content (Si/Al = 1.2-2.3). The zeolites are prepared by an environmentally friendly synthetic approach from precursor suspensions without using any organic template. Cellular interactions with the two types of zeolite nanocrystals are evaluated by cell viability, reactive oxygen species and cell life cycle assays. It is found that various concentrations of zeolites have negligible effects on the cell life cycle. Moreover, the LTL-and EMT-types zeolites did not cause extensive oxidative stress on the cells. Although it is seen that the zeolites extensively entered in the cells, there is no sign of toxicity for all employed concentrations of ultra-small EMT and LTL zeolites. Additionally, no abnormality in DNA replication while exposed to the zeolites is observed. Very importantly, the zeolite corona shows a high affinity for fibrinogen, moderate affinity for apoA-II and complement factor 3, and trace affinity for albumin, which is the most abundant protein of human plasma. Thus the zeolite nanoparticles can be considered as very promising material for purification of fibrinogen and lipoproteins. Since fibrinogen is considered as acute phase protein and found to be the most associated biomolecule in the composition of corona at the surface of zeolites, we propose that these nanoparticles can be potentially pro-inflammatory for in vivo applications. † Electronic supplementary information (ESI) available. See

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).…”

<p>Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on Medical Interventions</p>

“…Despite the significant cellular uptake of zeolites, none of the employed ultra-small EMT and LTL zeolites, at any concentrations, induced cytotoxicity ( Figure 3). 38 By the intervention of synthesis methods, the concern around cytotoxicity has shifted towards nanoscale materials. Microscale zeolites have been demonstrated to be safe and non-toxic; whereas, zeolite NPs have not yet been completely scrutinized regarding their cytotoxicity.…”

“…Among them, EMT-corona incubated with 100% human plasma displayed a very high affinity for fibrinogen and a very low affinity for albumin. 38 Zeolites that have been utilized for numerous years by US forces in Iraq and Afghanistan to induce coagulation and to stabilize life-threatening injuries, in the form of Ca-zeolite, have demonstrated to be dressed by protein corona, abundantly with thrombin. Their discovery emphasized the connection of the biomolecules in the protein corona with the procoagulant activity of the zeolite particles picturing a bright future for the hemostatic mechanisms of zeolite nanomaterials.…”

Ultrasmall Zeolite L Crystals Prepared from Highly Interdispersed Alkali‐Silicate Precursors

“…Syntheses of zeolite L tend to produce approximately 3 μm crystals (Figure S1). Methods for generating small zeolite L crystals often require long crystallization time (e.g., 18–48 h) and/or the use of microwave synthesis or unconventional reagents (e.g., aluminum foil and rice husk) that are not readily employed in commercial processes. In this study, we observe that the optimization of growth mixtures using potassium silicate yields ultrasmall zeolite L crystals with average sizes that are smaller than the majority of reported cases (Table S2 and Figures S3–S8).…”