Non-labeled monitoring of targeted liposome interactions with a model receptor surface: Effect of flow rate and water content

In this study, we present a novel in vitro approach that utilizes two surface-sensitive and label-free techniques, i.e. surface plasmon resonance (SPR) and quartz crystal microbalance (QCM), to study the interfacial events during liposome–target surface interactions. The flow channels of SPR and QCM devices were first synchronized via hydrodynamic modeling. Biotin–streptavidin was used as a model pair and self-assembled monolayers (SAMs) were utilized as model surfaces for targeted liposome–surface interaction studies. The interactions between biotin–liposomes and the streptavidin–biotin–SAM surfaces were investigated under controlled shear flows using the synchronized SPR and QCM devices. The response of the liposome interaction was monitored as a function of the flow rate. The affinity and the amount of bound liposome indicated that the increased flow rate improved the binding of the targeted liposomes to the model membrane surfaces. The combined use of the synchronized SPR and QCM devices for nanoparticle interaction studies clearly demonstrates the effect of the flow rate (or the shear stress) on the liposome binding. Our results suggest that the binding of liposomes to the model membranes is flow rate and shear stress regulated. Thus, the flow rate (or the shear stress), which is usually neglected, should be taken into account during the development and optimization of targeted liposome formulations. In addition, the water content within the liposome layer (including the water inside the liposomes and the water between the liposomes) had a significant influence on the visco-elasticity and the binding kinetics to the SAM surfaces.