| 1. |
- Nugroho, Ferry, 1986, et al.
(author)
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Topographically Flat Nanoplasmonic Sensor Chips for Biosensing and Materials Science
- 2017
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In: ACS Sensors. - : American Chemical Society (ACS). - 2379-3694. ; 2:1, s. 119-127
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Journal article (peer-reviewed)abstract
- Nanoplasmonic sensors typically comprise arrangements of noble metal nanoparticles on a dielectric support. Thus they are intrinsically characterized by surface topography with corrugations at the 10–100 nm length scale. While irrelevant in some bio- and chemosensing applications, it is also to be expected that the surface topography significantly influences the interaction between solids, fluids, nanoparticles and (bio)molecules, and the nanoplasmonic sensor surface. To address this issue, we present a wafer-scale nanolithography-based fabrication approach for high-temperature compatible, chemically inert and topographically flat and laterally homogeneous nanoplasmonic sensor chips. We demonstrate their sensing performance on three different examples, for which we also carry out a direct comparison with a traditional nanoplasmonic sensor with representative surface corrugation. Specifically, we (i) quantify the film-thickness dependence of the glass transition temperature in poly(methyl metacrylate) thin films, (ii) characterize the adsorption and specific binding kinetics of the avidin – b-BSA protein system and (iii) analyze supported lipid bilayer formation on SiO2 surfaces.
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| 2. |
- Claesson, Maria, 1985, et al.
(author)
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Pore Spanning Lipid Bilayers on Mesoporous Silica Having Varying Pore Size
- 2011
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In: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 27:14, s. 8974-8982
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Journal article (peer-reviewed)abstract
- Synthetic lipid bilayers have similar properties as cell membranes and have been shown to be of great use in the development of novel biomimicry devices. In this study, lipid bilayer formation on mesoporous silica of varying pore size, 2, 4, and 6 nm, has been investigated using quartz crystal microbalance with dissipation monitoring (QCM-D), fluorescent recovery after photo bleaching (FRAP), and atomic force microscopy (AFM). The results show that pore-spanning lipid bilayers were successfully formed regardless of pore size. However, the mechanism of the bilayer formation was dependent on the pore size, and lower surface coverages of adsorbed lipid vesicles were required on the surface having the smallest pores. A similar trend was observed for the lateral diffusion coefficient (D) of fluorescently labeled lipid molecules in the membrane, which was lowest on the surface having the smallest pores and increased with the pore size. All of the pore size dependent observations are suggested to be due to the hydrophilicity of the surface, which decreases with increased pore size.
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| 3. |
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| 4. |
- Fang, Zhao, 1986, et al.
(author)
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TiO2 nanoparticle interactions with supported lipid membranes – an example of removal of membrane patches
- 2016
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In: RSC Advances. - 2046-2069. ; 6:94, s. 91102-91110
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Journal article (peer-reviewed)abstract
- There is a need for different levels of model systems for effect studies of engineered nanoparticles and the development of nanoparticle structure–activity relationships in biological systems. Descriptors for nanoparticles based on their interactions in molecular model systems may become useful to predict toxicological responses of the nanoparticles in cells. Towards this end, we report on nanoparticle-induced formation of holes in supported model membranes. Specifically, TiO2 nanoparticle – lipid membrane interactions were studied under low ionic strength, basic conditions (pH 8), using different membrane compositions and several surface-sensitive analytical techniques. It was found that for mixed POPC/POPG (PG fractions ≥ 35%) membranes on silica supports, under conditions where electrostatic repulsion was expected, the addition of TiO2 nanoparticles resulted in transient interaction curves, consistent with the removal of part of the lipid membrane. The formation of holes was inferred from quartz crystal microbalance with dissipation (QCM-D) monitoring, as well as from optical measurements by reflectometry, and also verified by atomic force microscopy (AFM) imaging. The interaction between the TiO2 nanoparticles and the PG-containing membranes was dependent on the presence of Ca2+ ions. A mechanism is suggested where TiO2 nanoparticles act as scavengers of Ca2+ ions associated with the supported membrane, leading to weakening of the interaction between the membrane and the support and subsequent removal of lipid mass as TiO2 nanoparticles spontaneously leave the surface. This mechanism is consistent with the observed formation of holes in the supported lipid membranes.
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| 5. |
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| 6. |
- Frost, Rickard, 1979, et al.
(author)
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Acoustic detection of melanosome transport in Xenopus laevis melanophores
- 2013
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In: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 435:1, s. 10-18
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Journal article (peer-reviewed)abstract
- Organelle transport studies are often performed using melanophores from lower vertebrates due to the ease of inducing movements of pigment granules (melanosomes) and visualizing them by optical microscopy. Here, we present a novel methodology to monitor melanosome translocation (which is a light-sensitive process) in the dark using the quartz crystal microbalance with dissipation monitoring (QCM-D) technique. This acoustic sensing method was used to study dispersion and aggregation of melanosomes in Xenopus laevis melanophores. Reversible sensor responses, correlated to optical reflectance measurements, were obtained by alternating addition and removal of melatonin (leading to melanosome aggregation) and melanocyte-stimulating hormone (MSH) (leading to melanosome dispersion). By confocal microscopy, it was shown that a vertical redistribution of melanosomes occurred during the dispersion/aggregation processes. Furthermore, the transport process was studied in the presence of cytoskeleton-perturbing agents disrupting either actin filaments (latrunculin) or microtubules (nocodazole). Taken together, these experiments suggest that the acoustic responses mainly originate from melanosome transport along actin filaments (located close to the cell membrane), as expected based on the penetration depth of the QCM-D technique. The results clearly indicate the potential of QCM-D for studies of intracellular transport processes in melanophores.
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| 7. |
- Frost, Rickard, 1979, et al.
(author)
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Bioreducible insulin-loaded nanoparticles and their interaction with model lipid membranes
- 2011
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In: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 362:2, s. 575-583
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Journal article (peer-reviewed)abstract
- To improve design processes in the field of nanomedicine, in vitro characterization of nanoparticles with systematically varied properties is of great importance. In this study, surface sensitive analytical techniques were used to evaluate the responsiveness of nano-sized drug-loaded polyelectrolyte complexes when adsorbed to model lipid membranes. Two bioreducible poly(amidoamine)s (PAAs) containing multiple disulfide linkages in the polymer backbone (SS-PAAs) were synthesized and used to form three types of nanocomplexes by self-assembly with human insulin, used as a negatively charged model protein at neutral pH. The resulting nanoparticles collapsed on top of negatively charged model membranes upon adsorption, without disrupting the membrane integrity. These structural rearrangements may occur at a cell surface which would prevent uptake of intact nanoparticles. By the addition of glutathione, the disulfide linkages in the polymer backbone of the SS-PAAs were reduced, resulting in fragmentation of the polymer and dissociation of the adsorbed nanoparticles from the membrane. A decrease in ambient pH also resulted in destabilization of the nanoparticles and desorption from the membrane. These mimics of intracellular environments suggest dissociation of the drug formulation, a process that releases the protein drug load, when the nanocomplexes reaches the interior of a cell. (C) 2011 Elsevier Inc. All rights reserved.
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| 8. |
- Frost, Rickard, 1979, et al.
(author)
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Characterization of nanoparticle-lipid membrane interactions using QCM-D
- 2013
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In: Methods in Molecular Biology. - Totowa, NJ : Humana Press. - 1940-6029 .- 1064-3745. - 9781627033350 ; 991, s. 127-137
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Book chapter (other academic/artistic)abstract
- In vitro characterization of nanoparticles is becoming increasingly important due to the rapid development of novel nanoparticle formulations for applications in the field of nanomedicine and related areas. Commonly, nanoparticles are simply characterized with respect to their size and zeta potential, and additional in vitro characterization of nanoparticles is needed to develop useful nanoparticle structure-activity relationships. In this context it is highly interesting to characterize the interactions between nanoparticles and model interfaces, such as lipid membranes. Here, we describe a methodology to study such interactions using the quartz crystal microbalance with dissipation monitoring technique (QCM-D). In order to mimic some aspects of the native cell membrane, a supported lipid membrane is formed on the QCM-D sensor surface. Subsequently the membrane is exposed to nanoparticles, and the nanoparticle-lipid membrane interactions are monitored in real time. The outcome of such analysis provides information on the adsorption process (importantly kinetics and adsorbed amounts) as well as on the integrity of both the nanoparticles and the lipid membrane upon interaction. QCM-D analyses are suitable for screening of nanoparticle-lipid membrane interactions due to the fair throughput of the technique, which can be complemented, when needed, by additional analyses by other surface-sensitive analytical techniques.
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| 9. |
- Frost, Rickard, 1979, et al.
(author)
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Core−Shell Nanoplasmonic Sensing for Characterization of Biocorona Formation and Nanoparticle Surface Interactions
- 2016
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In: ACS Sensors. - : American Chemical Society (ACS). - 2379-3694. ; 1:6, s. 798-806
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Journal article (peer-reviewed)abstract
- Surface properties of nanoparticles imposed by particle size, shape, and surface chemistry are key features that largely determine their environmental fate and effects on biological systems. Consequently, development of analytical tools to characterize surface properties of nanomaterials and their relation to toxicological properties must occur in parallel with applications. As a contribution to this quest, we present a nanoplasmonic sensing strategy that enables systematic in situ characterization of molecule−nanoparticle interactions under well-controlled conditions, in terms of both nanoparticle size and surface chemistry, with particular focus on the importance of surface faceting in crystalline nanoparticles. We assess the performance of our sensing strategy by presenting two case studies. (i) The first is protein corona formation on faceted Au core−SiO2 shell nanoparticles of different sizes, and thus different surface facet-to-edge ratios. Based on 2D and 3D models of the investigated structures, we find that for small particles the curved regions between adjacent facets dominate the response of the corona formation process, whereas the facets dominate the response in the large particle regime. (ii) The second is in situ functionalization of Au core−SiO2 shell nanoparticle surfaces, and analysis of the subsequent protein repellent behavior. Due to the versatility of the presented sensing strategy in studies of nanoparticle surface properties, including in situ surface modifications, and their interactions with (bio)molecules during corona formation, we foresee it to become a valuable tool in the areas of nanomedicine and nanotoxicology.
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| 10. |
- Frost, Rickard, 1979, et al.
(author)
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Graphene Oxide and Lipid Membranes: Interactions and Nanocomposite Structures
- 2012
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In: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 12:7, s. 3356-3362
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Journal article (peer-reviewed)abstract
- We have investigated the interaction between graphene oxide and lipid membranes, using both supported lipid membranes and supported liposomes. Also, the reverse situation, where a surface coated with graphene oxide was exposed to liposomes in solution, was studied. We discovered graphene oxide-induced rupture of preadsorbed liposomes and the formation of a nanocomposite, bio-nonbio multilayer structure, consisting of alternating graphene oxide monolayers and lipid membranes. The assembly process was monitored in real time by two complementary surface analytical techniques (the quartz crystal microbalance with dissipation monitoring technique (QCM-D) and dual polarization interferometry (DPI)), and the formed structures were imaged with atomic force microscopy (AFM). From a basic science point of view, the results point toward the importance of electrostatic interactions between graphene oxide and lipid headgroups. Implications from a more practical point of view concern structure activity relationship for biological health/safety aspects of graphene oxide and the potential of the nanocomposite, multilayer structure as scaffolds for advanced biomolecular functions and sensing applications.
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| 11. |
- Frost, Rickard, 1979, et al.
(author)
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Graphene Oxide and Lipid Membranes: Size-Dependent Interactions
- 2016
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In: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 32:11, s. 2708-2717
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Journal article (peer-reviewed)abstract
- We have investigated the interaction of graphene oxide (GO) sheets with supported lipid membranes with focus on how the interaction depends on GO sheet size (three samples in the range of 90-5000 nm) and how it differs between small and large liposomes. The layer by-layer assembly of these materials into multilamellar structures, as discovered in our previous research, is now further explored. The interaction processes were monitored by two complementary, real time, surface-sensitive analytical techniques: quartz crystal microbalance with dissipation monitoring (QCM-D, electroacoustic sensing) and indirect nanoplasmonic sensing (INPS, optical sensing). The results show that the sizes of each of the two components, graphene oxide and liposomes, are important parameters affecting the resulting multilayer structures. Spontaneous liposome rupture onto graphene oxide is obtained for large lateral dimensions of the graphene oxide sheets.
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| 12. |
- Frost, Rickard, 1979
(author)
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In vitro characterization of nanodrugs at model lipid membranes
- 2010
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Licentiate thesis (other academic/artistic)abstract
- The use of nano-sized drug carriers to improve the efficiency of drug delivery has become well established during the past decades. New nanoparticle (NP) formulations for the administration of biopharmaceuticals (e.g. proteins and peptides) emerge at an increasing rate and the need for methods to evaluate their properties is expanding. Rational design of drug carriers requires understanding of their biophysical interactions with various biological barriers, e.g. cell membranes, mucus layers, or the blood brain barrier, since most carriers aim to deliver drugs across one or more of such barriers. The shape of NPs and the way they adhere to the cell membrane are important determinants for triggering of endocytosis. Another important NP parameter is their responsiveness to changes in the ambient environment when entering intracellular compartments e.g. the endosome or the cytosol. In this thesis, an in vitro screening platform for studying of NP – lipid membrane interaction is presented and used to characterize insulin-loaded polymeric NPs with respect to their interaction with differently charged supported lipid bilayers. By combining different surface sensitive techniques (quartz crystal microbalance with dissipation monitoring, reflectometry, and atomic force microscopy), structural properties of nano-sized polyelectrolyte complexes upon adsorption to model membranes were studied. From the results it is clear that electrostatic forces are important for the outcome of the NP-lipid membrane adsorption process. Polyelectrolyte complexes, which are non covalent assemblies of oppositely charged polyions, adopted different shapes on different membranes. Upon strong electrostatic attraction between the NPs and the membrane, NPs collapsed into a thin layer on top of an oppositely charged model membrane. This rearrangement process is potentially unfavorable for uptake into epithelial cells through endocytosis. NPs based on polymers with disulfide linkages in the polymer backbone were responsive to reducing agents. This property was shown by exposing membrane-adsorbed bioreducible poly(amido amine) based polyelectrolyte complexes to glutathione, mimicking an intracellular reductive environment. Similarly, the responsiveness of the NPs towards a decrease in ambient pH, mimicking the low pH in the late endosome, was shown. These results show the application of an experimental platform based on engineered supported lipid membranes and surface sensitive analytical techniques to evaluate drug carriers with respect to their membrane interactions as well as their responsiveness. The information gained from screening of novel drug carries gives important guidance during the process of design and development. An important next step in the development of the presented platform will be to establish a correlation to in vitro cell culture assays. NPs for other purposes could also be evaluated.
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| 13. |
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| 14. |
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| 15. |
- Frost, Rickard, 1979
(author)
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Probing the Nano-Bio Interface Using Surface Based Analytical Techniques
- 2012
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Doctoral thesis (other academic/artistic)abstract
- In recent years, the use of manufactured nanomaterials has been rapidly increasing in a wide range of application areas. Among others, these areas of application include cosmetics, medicine, clothing, and sporting goods. The small size of nanomaterials offers unique properties that are not possible to obtain by the same material in bulk. Although the use of nanomaterials holds great promises for society, the increased use and production also increases the concern that engineered nanomaterials may have adverse effects on human health or the environment.Unlike chemical substances, which have a defined structure and mass, nanomaterials need to be described by a large number of descriptors, e.g., size distribution, shape, and composition. In addition, to address possible effects on humans or the environment, it is of great importance to determine how nanomaterials interact with biological matter. Interactions with proteins, cell membranes, and cells may cause protein coronas, cellular uptake, or biocatalytic processes. To fully characterize such interactions there is a strong need for novel analytical techniques or methodologies.In this thesis, I have investigated how the lipid membrane, one of the most vital structures of a cell, interacts with various types of nanomaterials (e.g. polyelectrolyte complexes, graphene oxide, and TiO2 nanoparticles). The interactions between the model membranes and the nanomaterials have been studied using several complementary surface sensitive techniques. The results have showed conformational changes of polyelectrolyte complexes upon adsorption to the membranes and triggered disintegration of such complexes upon exposure to an acidic or a reducing environment. Furthermore, TiO2 nanoparticles have been shown to be able to disrupt lipid membranes in a Ca2+-mediated mechanism and a novel nanocomposite material, composed of alternating layers of graphene oxide and lipid membranes, has been prepared. In addition, the quartz-crystal microbalance with dissipation monitoring technique (QCM-D) has been explored in studies of intracellular transport processes using living cells. Specifically, pigment translocation in Xenopus laevis melanophores, has been shown to generate significant QCM-D responses. By using the described methodology, it is possible to evaluate the nanoparticle design and study how nanomaterials behave at a biological interface or effect specific cellular functions.
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| 16. |
- Frost, Rickard, 1979, et al.
(author)
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Real-time in situ analysis of biocorona formation and evolution on silica nanoparticles in defined and complex biological environments
- 2017
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In: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3372 .- 2040-3364. ; 9:10, s. 3620-3628
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Journal article (peer-reviewed)abstract
- Biomolecules such as proteins immediately adsorb on the surface of nanoparticles upon their exposure to a biological environment. The formed adlayer is commonly referred to as biomolecule corona (biocorona) and defines the biological activity and toxicity of the nanoparticle. Therefore, it is essential to understand in detail the biocorona formation process, and how it is governed by parameters like composition of the biological environment, and nanoparticle size, shape and faceting. Here we present a detailed equilibrium and real time in situ study of biocorona formation at SiO2-nanoparticle surfaces upon exposure to defined (BSA, IgG) and complex (bovine serum, IgG depleted bovine serum) biological samples. We use both nanofabricated surface-associated Au core-SiO2 shell nanoparticles (faceted, d = 92-167 nm) with integrated nanoplasmonic sensing function and dispersed SiO2 nanoparticles (using DLS and SDS-PAGE). The results show that preadsorbed BSA or IgG are exchanged for other proteins when exposed to bovine serum. In addition, the results show that IgG forms a biocorona with different properties at curved (edge) and flat (facet) SiO2-nanoparticle surfaces. Our study paves the way for further real time in situ investigations of the biocorona formation and evolution kinetics, as well as the role of molecular orientation in biocorona formation, on nanoparticles with surface faceting.
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| 17. |
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| 18. |
- Frost, Rickard, 1979, et al.
(author)
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Structural Rearrangements of Polymeric Insulin-loaded Nanoparticles Interacting with Surface-Supported Model Lipid Membranes
- 2011
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In: Journal of Biomaterials and Nanobiotechnology. - 2158-7027. ; 2:2, s. 181-193
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Journal article (peer-reviewed)abstract
- The design and screening of nanoparticles for therapeutic applications (nanodrugs) belong to an emerging research area, where surface based analytical techniques are promising tools. This study reports on the interaction of electro- statically assembled nanoparticles, developed for non-invasive administration of human insulin, with cell membrane mimics. Interactions between the nanoparticles and differently charged surface-supported model membranes were studied in real-time with the quartz crystal microbalance with dissipation monitoring (QCM-D) technique, in some ex- periments combined with optical reflectometry. Based on the experimental observations, we conclude that structural rearrangements of the nanoparticles occur upon adsorption to negatively charged lipid membranes.␣ The degree of structural changes in the nanoparticles will have important implications for the induced release of the protein drug load. The presented results provide an example of how a surface-based experimental platform can be used to charac- terize the physico-chemical properties of nanosized drug carriers with respect to their interactions at different surfaces.
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| 19. |
- Zhao, Fang, et al.
(author)
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TiO2 nanoparticle interactions with supported lipid membranes – an example of removal of membrane patches
- 2016
-
In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 6:94, s. 91102-91110
-
Journal article (peer-reviewed)abstract
- There is a need for different levels of model systems for effect studies of engineered nanoparticles and the development of nanoparticle structure–activity relationships in biological systems. Descriptors for nanoparticles based on their interactions in molecular model systems may become useful to predict toxicological responses of the nanoparticles in cells. Towards this end, we report on nanoparticle-induced formation of holes in supported model membranes. Specifically, TiO2 nanoparticle – lipid membrane interactions were studied under low ionic strength, basic conditions (pH 8), using different membrane compositions and several surface-sensitive analytical techniques. It was found that for mixed POPC/POPG (PG fractions ≥ 35%) membranes on silica supports, under conditions where electrostatic repulsion was expected, the addition of TiO2 nanoparticles resulted in transient interaction curves, consistent with the removal of part of the lipid membrane. The formation of holes was inferred from quartz crystal microbalance with dissipation (QCM-D) monitoring, as well as from optical measurements by reflectometry, and also verified by atomic force microscopy (AFM) imaging. The interaction between the TiO2 nanoparticles and the PG-containing membranes was dependent on the presence of Ca2+ ions. A mechanism is suggested where TiO2 nanoparticles act as scavengers of Ca2+ ions associated with the supported membrane, leading to weakening of the interaction between the membrane and the support and subsequent removal of lipid mass as TiO2 nanoparticles spontaneously leave the surface. This mechanism is consistent with the observed formation of holes in the supported lipid membranes.
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