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    Liposomes embedded in layer by layer constructs as simplistic extracellular vesicles transfer model

    Year: 2021

    Journal: Mater. Sci. Eng. C-Mater. Biol. Appl., Volume 121, FEB

    Authors: Dominguez-Arca, Vicente; Costa, Rui R.; Carvalho, Ana M.; Taboada, Pablo; Reis, Rui L.; Prieto, Gerardo; Pashkuleva, Iva

    Organizations: Programa Iacobus; Portuguese Fundacao para a Ciencia e a Tecnologia [PTDC/BTM-MAT/28327/2017, CEE-CIND/02842/2017, SFRH/BD/114847/2016]; European Commission [ELASTISLET NMP-2014-646075, FORECAST 668983]; Spanish AEI; European Regional Development Fund [MAT2016-80266-R]; Ministerio de Economia y Competitividad of Spain [MAT2016-80266-R]; Xunta de Galicia (Grupo de Referencia Competitiva) [ED431C 2018/26]; Xunta de Galicia (Agrupacion Estrategica de Materiales-AEMAT) [ED431E 2018/08]

    Keywords: Layer-by-layer; Liposomes; Glycosaminoglycans; Supported vesicle layers; Extracellular matrix; Cell communication

    Extracellular vesicles (EVs) are particles originating from the exfoliation of the cellular membrane. They are involved in cell-to-cell and cell-to-matrix signaling, exchange of bioactive molecules, tumorigenesis and metastasis, among others. To mitigate the limited understanding of EVs transfer phenomena, we developed a simplistic model that mimics EVs and their interactions with cells and the extracellular matrix. The proposed model is a layer by layer (LbL) film built from the polycationic poly-L-lysine (PLL) and the glycosaminoglycan hyaluronic acid (HA) to provide ECM mimicry. Positively charged 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and N-1 ,N-1 ,N-14 ,N-14-tetramethyl-N-1,N-14 -ditetradecyltetradecane-1,14-diaminium dibromide (GS14) liposomes were embedded in this construct to act as EVs analogs. To simulate EVs carrying substances, Nile Red was loaded as a model of lipophilic cargo molecules. The integration of each component was followed by quartz crystal microbalance measurements, which confirmed the immobilization of intact liposomes on the underlying (PLL/HA)(3) soft film. The release of Nile Red from liposomes either embedded in the LbL construct or exposed at its surface revealed a fast first order release. This system was validated as a model for EV/cell interactions by incubation with breast cancer cells MDA-MB-231. We observed higher internalization for embedded liposomes when compared with surface-exposed ones, showcasing that the ECM mimic layers do not constitute a barrier to liposome/cell interactions but favor them.
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