Mesoporous Silica Nanoparticles for Reducing Hemolytic Activity Towards Mammalian Red Blood Cells

Slowing, Igor I.; Wu, Kevin C.‐W.; Vivero‐Escoto, Juan L.; Lin, Victor S.-Y.

doi:10.1002/smll.200800926

Cited by 516 publications

(442 citation statements)

References 31 publications

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“…30 These results were later confirmed by Lin and Haynes, who demonstrated that the hemocompatibility of MSNs also depended on the size of the nanoparticles. 31 These findings were mainly based on hemolysis assays performed by UV-vis spectroscopy.…”

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confidence: 66%

“…[43][44][45][46][47] The occurrence of the interaction depends on whether the amount of energy released from the binding of the MSNs with the RBC membrane (E i ) is able to overcome the amount of free energy required to bend the membrane and adapt to the surface of MSNs (E b ). The former energy is associated with the external surface area (i.e., accessible silanols) of MSN, 30 while the latter is proportional to the curvature or inversely proportional to the square of the radius (r) of the particle. 43,44,47 The external surface areas of s-MSNs and l-MSNs, calculated from the t plots of their N 2 adsorption isotherms, 48 were 81.6 and 155.4 m 2 g -1 , respectively.…”

Section: Resultsmentioning

confidence: 99%

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Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

Zhao¹,

Sun²,

Zhang³

et al. 2011

ACS Nano

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The interactions of mesoporous silica nanoparticles (MSNs) of different particle sizes and surface properties with human red blood cell (RBC) membranes were investigated by membrane filtration, flow cytometry, and various microscopic techniques. Small MCM-41-type MSNs (∼100 nm) were found to adsorb to the surface of RBCs without disturbing the membrane or morphology. In contrast, adsorption of large SBA-15-type MSNs (∼600 nm) to RBCs induced a strong local membrane deformation leading to spiculation of RBCs, internalization of the particles, and eventual hemolysis. In addition, the relationship between the degree of MSN surface functionalization and the degree of its interaction with RBC, as well as the effect of RBC−MSN interaction on cellular deformability, were investigated. The results presented here provide a better understanding of the mechanisms of RBC−MSN interaction and the hemolytic activity of MSNs and will assist in the rational design of hemocompatible MSNs for intravenous drug delivery and in vivo imaging. R ecent advancements in particle size and morphology control of mesoporous materials have led to the creation of nano-and submicrometer-sized mesoporous silica nanoparticles (MSNs). [1][2][3][4][5] The MSN materials with well-ordered cylindrical pore structures, such as MCM-41 and SBA-15, have attracted special interest in the biomedical field. 1 The large surface areas and pore volumes of these materials allow the efficient adsorption of a wide range of molecules, including small drugs, 6-10 therapeutic proteins, 11-13 antibiotics, 14,15 and antibodies. 16 Therefore, these materials have been proposed for use as potential vehicles for biomedical imaging, real-time diagnosis, and controlled delivery of multiple therapeutic agents. [6][7][8]10,[17][18][19][20][21][22][23][24][25] Despite the considerable interest in the biomedical applications of MSNs, relatively few studies have been published on the biocompatibility of the two most common types of MSNs (MCM-41 and SBA-15). [26][27][28][29] Asefa and co-workers reported that the cellular bioenergetics (cellular respiration and ATP levels) were inhibited remarkably by large SBA-15 nanoparticles, but the inhibition was greatly reduced by smaller MCM-41-type nanoparticles. 26 These differences in the disruption of cellular bioenergetics are believed to be caused by the different surface areas, number of surface silanol groups, and/or particle sizes of both types of material. A recent study by Kohane and collaborators on the systemic effects of MCM-41 (particle size ∼150 nm) and SBA-15 (particle size ∼800 nm) MSNs in live animals revealed interesting findings regarding their biocompatibility. 27 While large doses of mesoporous silicas administered subcutaneously to mice appear to be relatively harmless, the same doses given intravenously or intraperitoneally were lethal. 27 A possible reason for the severe systemic toxicity of MSNs when injected intravenously could be the interactions of the nanoparticles with blood cells.Our initial studies...

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confidence: 66%

Section: Resultsmentioning

confidence: 99%

Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

Zhao¹,

Sun²,

Zhang³

et al. 2011

ACS Nano

Self Cite

504

440

View full text Add to dashboard Cite

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“…13,29 As the hemolytic effect of negatively charged silica was practically the same when samples were normalized by specific surface area, it is possible to conclude that not only the negative zeta potential must be considered as the responsible for the citotoxicity of the nanoparticles, once sample Si-P(CH 3 )O 3 H possesses a more negatively charged surface. In this way, other mechanisms and interactions such as ROS, hydrogen bonds and van der Waals forces must be considered as responsible for the citotoxicity observed here.…”

Section: Resultsmentioning

confidence: 96%

“…Firstly, it was observed that silanol groups on mesoporous silica structures induce less hemolytic effect compared to rigid spherical nanoparticles possibly due to shape-induced effects, which determine the spatial availability of silanols on the nanoparticle-cell interface. 13 Further, it was observed that: (i) smaller Stöber silica nanoparticles (24 nm) induce a pronounced hemolytic effect when compared with bigger ones (263 nm); 14 (ii) nanostructures with high aspect ratio (nanorods) are more cytotoxic than spherical nanoparticles; 15 (iii) mesoporous silica nanostructures (MSNs) with ordered pores (MCM-41) induce a stronger hemolytic effect compared with non-ordered; 14 (iv) small mesoporous nanoparticles (20 nm) consisted of ethenylenebridged silsesquioxane present very low toxicity 16 and (v) polymers such as PEG (polyethylene glycol) can be used to coat particles in order to greatly reduce the hemolysis. 17 Furthermore, an extensive assessment of the interaction of bare and functionalized porous silica nanomaterials with RBCs concluded that SBA-15-type MSNs cause the deformation of RBCs and consequently lead to their disruption.…”

Section: Introductionmentioning

confidence: 99%

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

Paula¹,

Martinez²,

Júnior³

et al. 2012

J. Braz. Chem. Soc.

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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...

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“…The biocompatibility of MSN both in vitro and in vivo has been demonstrated by several recent studies. [4][5][6][7] Furthermore, literature reports on the biodistribution and circulation properties of MSN administered in animals by intravenous injection have highlighted the promising potential of these multifunctional nanoparticles for in vivo biomedical applications and organ-specific delivery of therapeutics.…”

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confidence: 99%

Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP

et al. 2009

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A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices.

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Mesoporous Silica Nanoparticles for Reducing Hemolytic Activity Towards Mammalian Red Blood Cells

Cited by 516 publications

References 31 publications

Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

Interaction of Mesoporous Silica Nanoparticles with Human Red Blood Cell Membranes: Size and Surface Effects

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

Mesoporous Silica Nanoparticle-Based Double Drug Delivery System for Glucose-Responsive Controlled Release of Insulin and Cyclic AMP

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