Multifunctional Lipid/Quantum Dot Hybrid Nanocontainers for Controlled Targeting of Live Cells

Gopalakrishnan, Gopakumar; Danelon, Christophe; Izewska, Paulina; Prummer, Michael; Bolinger, Pierre-Yves; Geissbühler, Isabelle; Demurtas, Davide; Dubochet, Jacques; Vogel, Horst

doi:10.1002/anie.200600545

Cited by 211 publications

(160 citation statements)

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“…If this step does not occur, the single nanoparticles will remain in a stable micelle state, which generally coincides with previously documented observations. 18,19 Interestingly, this approach can be applied to different nanoparticle sizes: In an additional trial, we observed that nanoparticles with a mean core diameter of 7.2 ( 0.9 nm form similar structures, as well (Figure 5B), which shows that even nanoparticles up to 8.1 nm ( Figure 5B, inset) can be inserted between the liposomal bilayer by following this methodology.…”

Section: Resultsmentioning

confidence: 89%

“…18,20,22 On the other hand, spheres larger than approximately 6.5 nm in diameter, 22 or around the overall bilayer thickness in general, 13,23 rather induce lipid monolayer adsorption onto the surface and result in stable micelle-like structures. These norms have been repetitively validated in experimental studies, 18,19 and larger nanoparticles (i.e., >22 nm) in turn are known to be wrapped up by a lipid bilayer. 12,15 These boundaries can be cumbersome when designing application-oriented nanocontainers, as specific nanoparticle properties (i.e., optical, thermal and/or magnetic) ; which make them desirable in the first place ; are mostly governed by their size.…”

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confidence: 92%

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Insertion of Nanoparticle Clusters into Vesicle Bilayers

et al. 2014

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. z These authors contributed equally to this work.C ombining nanoparticles with liposomes is a highly elaborative methodology in the emerging fields of nanomedicine and nanobiotechnology. Not only can the well-known benefits 1 of liposomes be enhanced for specific applications, but their established scope of functionality (e.g., targeted drug delivery 2À7 ) can also be widely expanded to fulfill additional tasks and thereby act as eclectic toolboxes at a nanoscale. 8 Lipid bilayer membranes alone are significantly relevant materials for a broad range of academic disciplines. Their interactions with nanoparticles have been gradually studied over the past years, particularly in the context of nanoparticle transport across cellular membranes. 9À12 Notable experimental and theoretical studies have addressed different variables (e.g., the nanoparticle size or lipid composition) and their effects on adhesion and wrapping or nanoparticle-induced pore formation. 12À15 These concepts have been complemented by, for example, molecular dynamics simulations 16 or mesoscale thermodynamic modeling 13 and provide, among others, more accurate descriptions of phospholipid membranes to determine the role and effects of nanoparticles on lipid bilayers in general.In the context of stimuli-responsive liposomeÀnanoparticle hybrids for drug delivery, embedding hydrophobic nanoparticles directly within the liposomal lipid bilayer has become a popular approach. There are several standards in the literature on this subject, 17À21 which also present operative methodologies to accomplish this task. In this wide-ranging field, leading studies have focused on using very small nanoparticles * Address correspondence to alke.fink@unifr.ch. ABSTRACTA major contemporary concern in developing effective liposomeÀnanoparticle hybrids is the present inclusion size limitation of nanoparticles betw vesicle bilayers, which is considered to be around 6.5 nm in diameter. In this article, we present experimental observations backed by theore considerations which show that greater structures can be incorporated within vesicle membranes by promoting the clustering of nanoparticles be liposome formation. Cryo-transmission electron microscopy and cryo-electron tomography confirm these observations at unprecedented detail underpin that the liposome membranes can accommodate flexible structures of up to 60 nm in size. These results imply that this material is more vers in terms of inclusion capabilities and consequently widens the opportunities in developing multivalent vesicles for nanobiotechnology applications

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Section: Resultsmentioning

confidence: 89%

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confidence: 92%

Insertion of Nanoparticle Clusters into Vesicle Bilayers

et al. 2014

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“…31 In other work, qdots were localized inside or adjacent to cellular membranes by using vesicle delivery methods. 48 Membrane simulations also predict that, with proper surface chemistry, the localization of larger nanocrystals inside a bilipid layer can be free-energetically favorable. 49 However, developing surface chemistries capable of localizing large nanocrystals (R ~ 4 nm) specifically within neural membranes remains a substantial challenge.…”

Section: Discussionmentioning

confidence: 96%

Optical Strategies for Sensing Neuronal Voltage Using Quantum Dots and Other Semiconductor Nanocrystals

Marshall

Schnitzer

2013

ACS Nano

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Biophysicists have long sought optical methods capable of reporting the electrophysiological dynamics of large-scale neural networks with millisecond-scale temporal resolution. Existing fluorescent sensors of cell membrane voltage can report action potentials in individual cultured neurons, but limitations in brightness and dynamic range of both synthetic organic and genetically encoded voltage sensors have prevented concurrent monitoring of spiking activity across large populations of individual neurons. Here we propose a novel, inorganic class of fluorescent voltage sensors: semiconductor nanoparticles, such as ultrabright quantum dots (qdots). Our calculations revealed that transmembrane electric fields characteristic of neuronal spiking (~10 mV/nm) modulate a qdot's electronic structure and can induce ~5% changes in its fluorescence intensity and ~1 nm shifts in its emission wavelength, depending on the qdot's size, composition, and dielectric environment. Moreover, tailored qdot sensors composed of two different materials can exhibit substantial (~30%) changes in fluorescence intensity during neuronal spiking. Using signal detection theory, we show that conventional qdots should be capable of reporting voltage dynamics with millisecond precision across several tens or more individual neurons over a range of optical and neurophysiological conditions. These results unveil promising avenues for imaging spiking dynamics in neural networks and merit in-depth experimental investigation. Toward addressing these challenges, we studied whether tools from nanotechnology, specifically, bright, multifunctional semiconductor quantum dots (qdots), 22,23 might be useful for imaging neuronal membrane potentials. Qdots are known to possess voltagesensitive optical properties, including a red-shifting of the qdot's fluorescence emission peak, spectral broadening, and a decrease in the intensity of fluorescence emission ( Figure 1C,D). [24][25][26][27] Qdots also are highly resistant to photobleaching and exhibit large quantum yields and absorption cross sections for one-(σ 1 ) and two-photon (σ 2 ) excitation. For example, CdSe qdots with radius R ~ 3 nm exhibit cross sections of σ 1 > 1 nm 2 and σ 2 > 3 × 10 4 GM, as compared to σ 1 ~ 10 −2 nm 2 and σ 2 ~ 3 × 10 2 GM for green fluorescent protein. 28,29 Marshall and Schnitzer Page 2 ACS Nano. Author manuscript; available in PMC 2017 December 15. Graphical Abstract HHMI Author Manuscript HHMI Author Manuscript HHMI Author ManuscriptTo evaluate the spike detection capabilities of qdot indicators quantitatively, we applied a theoretical approach that incorporates the physical, biophysical, and statistical components of the problem. We calculated the effect of applied electric fields on the qdot's electronic structure and examined how this modulates a qdot's fluorescence intensity and emission spectra. We also studied nonspherical, nonhomogenous qdots, which we refer to more generally as semiconductor nanocrystals, and found that these nanoparticles can demonstrate muc...

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“…Owing to the additional layer bound by hydrophobic interactions, this coating strategy can be applied regardless of the material of the inorganic particle core. Variations include the embedding of hydrophobic quantum dots into the lipid bilayer of vesicles and liposomes (Gopalakrishnan et al 2006) and paramagnetic lipids that yield fluorescent nanoparticles with additional magnetic properties (Mulder et al 2006a,b).…”

Section: (C) Additional Coating Layersmentioning

confidence: 99%

Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles

Sperling

Parak

2010

Phil. Trans. R. Soc. A.

1,394

1,092

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Inorganic colloidal nanoparticles are very small, nanoscale objects with inorganic cores that are dispersed in a solvent. Depending on the material they consist of, nanoparticles can possess a number of different properties such as high electron density and strong optical absorption (e.g. metal particles, in particular Au), photoluminescence in the form of fluorescence (semiconductor quantum dots, e.g. CdSe or CdTe) or phosphorescence (doped oxide materials, e.g. Y 2 O 3 ), or magnetic moment (e.g. iron oxide or cobalt nanoparticles). Prerequisite for every possible application is the proper surface functionalization of such nanoparticles, which determines their interaction with the environment. These interactions ultimately affect the colloidal stability of the particles, and may yield to a controlled assembly or to the delivery of nanoparticles to a target, e.g. by appropriate functional molecules on the particle surface. This work aims to review different strategies of surface modification and functionalization of inorganic colloidal nanoparticles with a special focus on the material systems gold and semiconductor nanoparticles, such as CdSe/ZnS. However, the discussed strategies are often of general nature and apply in the same way to nanoparticles of other materials.

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Multifunctional Lipid/Quantum Dot Hybrid Nanocontainers for Controlled Targeting of Live Cells

Cited by 211 publications

References 70 publications

Insertion of Nanoparticle Clusters into Vesicle Bilayers

Insertion of Nanoparticle Clusters into Vesicle Bilayers

Optical Strategies for Sensing Neuronal Voltage Using Quantum Dots and Other Semiconductor Nanocrystals

Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles

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