scholarly journals Antibody-Hapten Recognition at the Surface of Functionalized Liposomes Studied by SPR: Steric Hindrance of Pegylated Phospholipids in Stealth Liposomes Prepared for Targeted Radionuclide Delivery

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Eliot. P. Botosoa ◽  
Mike Maillasson ◽  
Marie Mougin-Degraef ◽  
Patricia Remaud-Le Saëc ◽  
Jean-François Gestin ◽  
...  

Targeted PEGylated liposomes could increase the amount of drugs or radionuclides delivered to tumor cells. They show favorable stability and pharmacokinetics, but steric hindrance of the PEG chains can block the binding of the targeting moiety. Here, specific interactions between an antihapten antibody (clone 734, specific for the DTPA-indium complex) and DTPA-indium-tagged liposomes were characterized by surface plasmon resonance (SPR). Non-PEGylated liposomes fused on CM5 chips whereas PEGylated liposomes did not. By contrast, both PEGylated and non-PEGylated liposomes attached to L1 chips without fusion. SPR binding kinetics showed that, in the absence of PEG, the antibody binds the hapten at the surface of lipid bilayers with the affinity of the soluble hapten. The incorporation of PEGylated lipids hinders antibody binding to extents depending on PEGylated lipid fraction and PEG molecular weight. SPR on immobilized liposomes thus appears as a useful technique to optimize formulations of liposomes for targeted therapy.

Physchem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 133-151
Author(s):  
Philipp Grad ◽  
Katarina Edwards ◽  
Víctor Agmo Hernández

PEGylated lipid nanoparticles have a continuously expanding range of applications, particularly within pharmaceutical areas. Hereby, it is shown with the help of the Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) and other surface sensitive techniques that, at room temperature, PEGylated liposomes and lipodisks adhere strongly to silica surfaces resulting in the displacement of the hydration layer of silica and the formation of immobilized nanoparticle films. Furthermore, it is shown that drastic changes in the structure of the immobilized films occur if the temperature is increased to >35 °C. Thus, intact immobilized PEGylated liposomes rupture and spread, even in the gel phase state; immobilized lipodisks undergo complete separation of their components (bilayer forming lipids and PEGylated lipids) resulting in a monolayer of adsorbed PEGylated lipids; and PEGylated supported lipid bilayers release part of the water trapped between the lipid membrane and the surface. It is hypothesized that these changes occur mainly due to the changes in the configuration of PEG chains and a drastic decrease of the affinity of the polymer for water. The observed phenomena can be applied, e.g., for the production of defect-free supported lipid bilayers in the gel or liquid ordered phase states.


2018 ◽  
Author(s):  
Luke Jordan ◽  
Nathan Wittenberg

This is a comprehensive study of the effects of the four major brain gangliosides (GM1, GD1b, GD1a, and GT1b) on the adsorption and rupture of phospholipid vesicles on SiO2 surfaces for the formation of supported lipid bilayer (SLB) membranes. Using quartz crystal microbalance with dissipation monitoring (QCM-D) we show that gangliosides GD1a and GT1b significantly slow the SLB formation process, whereas GM1 and GD1b have smaller effects. This is likely due to the net ganglioside charge as well as the positions of acidic sugar groups on ganglioside glycan head groups. Data is included that shows calcium can accelerate the formation of ganglioside-rich SLBs. Using fluorescence recovery after photobleaching (FRAP) we also show that the presence of gangliosides significantly reduces lipid diffusion coefficients in SLBs in a concentration-dependent manner. Finally, using QCM-D and GD1a-rich SLB membranes we measure the binding kinetics of an anti-GD1a antibody that has similarities to a monoclonal antibody that is a hallmark of a variant of Guillain-Barre syndrome.


Soft Matter ◽  
2013 ◽  
Vol 9 (16) ◽  
pp. 4219-4226 ◽  
Author(s):  
Francesca Ruggeri ◽  
Fan Zhang ◽  
Tania Lind ◽  
Erica D. Bruce ◽  
Boris L. T. Lau ◽  
...  

2018 ◽  
Author(s):  
Merve Dogangun ◽  
Paul E. Ohno ◽  
Dongyue Liang ◽  
Alicia C. McGeachy ◽  
Ariana Gray Be ◽  
...  

<div> <div> <p>We report vibrational sum frequency generation (SFG) spectra in which the C–H stretches of lipid alkyl tails in fully hydrogenated single- and dual-component supported lipid bilayers are detected along with the O–H stretching continuum above the bilayer. As the salt concentration is increased from ~10 μM to 0.1 M, the SFG intensities in the O–H stretching region decrease by a factor of 2, consistent with significant absorptive-dispersive mixing between χ(2) and χ(3) contributions to the SFG signal generation process from charged interfaces. A method for estimating the surface potential from the second-order spectral lineshapes (in the OH stretching region) is presented and discussed in the context of choosing truly zero-potential reference states. Aided by atomistic simulations, we find that the strength and orientation distribution of the hydrogen bonds over the purely zwitterionic bilayers are largely invariant between sub-micromolar and hundreds of millimolar concentrations. However, specific interactions between water molecules and lipid headgroups are observed upon replacing phosphocholine (PC) lipids with negatively charged phosphoglycerol (PG) lipids, which coincides with SFG signal intensity reductions in the 3100 cm-1 to 3200 cm-1 frequency region. The atomistic simulations show that this outcome is consistent with a small, albeit statistically significant, decrease in the number of water molecules adjacent to both the lipid phosphate and choline moieties per unit area, supporting the SFG observations. Ultimately, the ability to probe hydrogen-bond networks over lipid bilayers holds the promise of opening paths for understanding, controlling, and predicting specific and non-specific interactions between membranes and ions, small molecules, peptides, polycations, proteins, and coated and uncoated nanomaterials.<br></p></div></div>


Author(s):  
Merve Dogangun ◽  
Paul E. Ohno ◽  
Dongyue Liang ◽  
Alicia C. McGeachy ◽  
Ariana Gray Be ◽  
...  

<div> <div> <p>We report vibrational sum frequency generation (SFG) spectra in which the C–H stretches of lipid alkyl tails in fully hydrogenated single- and dual-component supported lipid bilayers are detected along with the O–H stretching continuum above the bilayer. As the salt concentration is increased from ~10 μM to 0.1 M, the SFG intensities in the O–H stretching region decrease by a factor of 2, consistent with significant absorptive-dispersive mixing between χ(2) and χ(3) contributions to the SFG signal generation process from charged interfaces. A method for estimating the surface potential from the second-order spectral lineshapes (in the OH stretching region) is presented and discussed in the context of choosing truly zero-potential reference states. Aided by atomistic simulations, we find that the strength and orientation distribution of the hydrogen bonds over the purely zwitterionic bilayers are largely invariant between sub-micromolar and hundreds of millimolar concentrations. However, specific interactions between water molecules and lipid headgroups are observed upon replacing phosphocholine (PC) lipids with negatively charged phosphoglycerol (PG) lipids, which coincides with SFG signal intensity reductions in the 3100 cm-1 to 3200 cm-1 frequency region. The atomistic simulations show that this outcome is consistent with a small, albeit statistically significant, decrease in the number of water molecules adjacent to both the lipid phosphate and choline moieties per unit area, supporting the SFG observations. Ultimately, the ability to probe hydrogen-bond networks over lipid bilayers holds the promise of opening paths for understanding, controlling, and predicting specific and non-specific interactions between membranes and ions, small molecules, peptides, polycations, proteins, and coated and uncoated nanomaterials.<br></p></div></div>


2018 ◽  
Vol 516 ◽  
pp. 284-294 ◽  
Author(s):  
Costanza Montis ◽  
Viola Generini ◽  
Giulia Boccalini ◽  
Paolo Bergese ◽  
Daniele Bani ◽  
...  

2018 ◽  
Author(s):  
Luke Jordan ◽  
Nathan Wittenberg

This is a comprehensive study of the effects of the four major brain gangliosides (GM1, GD1b, GD1a, and GT1b) on the adsorption and rupture of phospholipid vesicles on SiO2 surfaces for the formation of supported lipid bilayer (SLB) membranes. Using quartz crystal microbalance with dissipation monitoring (QCM-D) we show that gangliosides GD1a and GT1b significantly slow the SLB formation process, whereas GM1 and GD1b have smaller effects. This is likely due to the net ganglioside charge as well as the positions of acidic sugar groups on ganglioside glycan head groups. Data is included that shows calcium can accelerate the formation of ganglioside-rich SLBs. Using fluorescence recovery after photobleaching (FRAP) we also show that the presence of gangliosides significantly reduces lipid diffusion coefficients in SLBs in a concentration-dependent manner. Finally, using QCM-D and GD1a-rich SLB membranes we measure the binding kinetics of an anti-GD1a antibody that has similarities to a monoclonal antibody that is a hallmark of a variant of Guillain-Barre syndrome.


2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Salma E. Ahmed ◽  
Hesham G. Moussa ◽  
Ana M. Martins ◽  
Mohammad H. Al-Sayah ◽  
Ghaleb A. Husseini

AbstractThe use of liposomes as carriers for chemotherapeutic agents in combination with ultrasound as a stimulus to control the time and space of the drug release is a promising approach for cancer treatment, as it can reduce the side effects caused by conventional chemotherapy. This in vitro study investigated the triggered release of calcein from stealth (PEGylated) and non-stealth (non-PEGylated) liposomes, using ultrasound at low (20 kHz) and high (1 and 3 MHz) frequencies, and at different power densities. Release was monitored by the increase in fluorescence due to relieving of calcein’s self-quenching upon dilution when the model drug leaks out of the liposomes. The results showed that, independent of the power density, the release was highest at 20 kHz. For the same frequency, release usually increased with increasing power densities. Additionally, for release at 20 kHz, a comparison was done for PEGylated and non-PEGylated liposomes, at two pH values: 5.2 and 7.4. The results were then compared to previously published studies. In all cases, the mechanism of release seems to involve cavitation events that either pierce a hole in or shear open the liposomes, as all the determined power densities are above the transient cavitation threshold.


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