Suppression of the hemolytic effect of mesoporous silica nanoparticles after protein corona interaction: independence of the surface microchemical environment

Abstract

Nanopartículas mesoporosas de sílica são conhecidas por induzirem hemólise de células vermelhas do sangue (RBCs) humano quando ensaios de citotoxicidade são feitos em solução-tampão de fosfato (PBS). Entretanto, em uma abordagem mais realista, a presença de biomoléculas do plasma sanguíneo precisa ser considerada em qualquer avaliação nanotoxicológica de nanopartículas porosas de SiO 2 quando se objetiva a sua utilização em aplicações biomédicas através de administração intravenosa. Nesse contexto, demonstrou-se neste trabalho que nanopartículas porosas de sílica não induzem nenhum efeito citotóxico em células vermelhas do sangue quando ensaios de hemólise são feitos na presença de plasma sanguíneo, independentemente da carga superficial (positiva ou negativa) da nanopartícula. A ausência de hemólise está principalmente associada à adsorção de proteínas do plasma sobre a superfície das nanopartículas, levando à formação de um recobrimento proteico estável (denominado protein corona ou PC) que blinda o ambiente microquímico original das nanopartículas.Mesoporous silica nanoparticles are known to induce the hemolysis of human red blood cells (RBCs) when citotoxicity assays are performed in a phosphate buffer solution (PBS). However, in a more realistic approach, the presence of blood plasma biomolecules must be considered in any nanotoxicological evaluation of porous SiO 2 nanoparticles when biomedical applications through intravenous administration are aimed. In this context, it is demonstrated in this work that porous silica nanoparticles do not induce any cytotoxic effect on RBCs when hemolysis assay is done in the presence of blood plasma, regardless the surface charge (positive or negative) of the nanoparticle. The absence of hemolysis is mainly associated with the adsorption of plasma proteins on the nanoparticle surface, which leads to the formation of a stable protein coating (called protein corona or PC) that shields the original microchemical environment of bare nanoparticles.Keywords: nanoparticles, SiO 2 , mesopores, hemolytic effect, protein corona IntroductionSince porous silica nanoparticles were elected as possible protagonists in a future revolution of several medical processes of theranosis, they have been widely studied during the last decade through the host-guest approach, thus resulting in promising perspectives mainly in the areas of detection 1-3 and treatment of tumors. [4][5][6][7] While part of the scientific community creatively advances towards the engineering of porous silica nanostructures, others are acting in a proactive approach by considering environmental and toxicological effects of nano-based silica materials. In the latter context, several in vitro citotoxicity assays indicated a very high biocompatibility of porous silica nanoparticles. [8][9][10] However, a desirable in vivo biocompatibility is not straightforward. For instance, it is well known that amorphous silica particles induce toxicity on human red blood cells (RBCs) and, consequently, this test is being used as a ke...

Monitoring the Hemolytic Effect of Mesoporous Silica Nanoparticles after Human Blood Protein Corona Formation

“…The pore volume, calculated from the single‐point value adsorbed at P / P 0 ≈ 0.94, is about 1 cm 3 g –1 . The pore diameter, calculated from the N 2 ‐sorption experiments through the Barrett–Joyner–Halenda (BJH) method is about 2 nm 7,28. This value is in very good agreement with the electron micrographs obtained through scanning‐transmission electron microscopy (STEM) in the high angular annular dark field mode (HAADAF; Figure 1 top right panel), which also revealed the pore size of the nanoparticles to be around 2 nm.…”

“…In the specific case of the protein corona formed from blood proteins, molecular biology and analytical biochemistry have precisely identified the composition of the protein coronas of several nanoparticles, and the hemolysis mitigation/suppression effect of the protein corona has been discussed 7,17,18. However, there is no information available on how much protein is necessary for mitigating the toxicity (i.e.…”

In vitro hematological and in vivo immunotoxicity assessment of dextran stabilized iron oxide nanoparticles

“…Another factor that may contribute to the non-hemolytic property of DIONPs is its propensity to form specific interactions with plasma proteins [20]. Formation of a plasma protein corona on NP surface has been shown to protect red blood cells from nanoparticlesmediated hemolysis [21,22].…”

Biological Requirement and Safety Assessment of Nanomedicines

“…79 When the assays are conducted in plasma, hemolysis did not take place regardless of the surface charge due to the formation of a protein corona which inhibits damage to erythrocytes. 80 Differences in hemolytic capacity were also detected between different NPs. For example Ag NPs exhibited a higher hemolytic capacity compared to Au NPs or Pt NPs.…”