Abstract
The continuous technological advancement of nanomedicine has enabled the development of novel vehicles for the effective delivery of therapeutic substances. Synthetic drug delivery systems are nano-sized carriers made from various materials that can be designed to deliver therapeutic cargoes to cells or tissues. However, rapid clearance by the immune system and the poor targeting profile of synthetic drug delivery systems are examples of the pressing obstacles faced in nanomedicine, which have directed the field toward the development of alternative strategies. Extracellular vesicles (EVs) are nanoscale particles enclosed by a protein-rich lipid bilayer; they are released by cells and are considered to be important mediators of intercellular communication. Owing to their natural composition, EVs have been suggested to exhibit good biocompatibility and to possess homing properties to specific cell types. Combining EVs with synthetic nanoparticles by defined hybridization steps gives rise to a novel potential drug delivery tool, i.e., EV-based hybrid systems. These novel therapeutic vehicles exhibit potential advantageous features as compared to synthetic drug delivery systems such as enhanced cellular uptake and cargo delivery, immuno-evasive properties, capability of crossing biological barriers, and tissue targeting profile. Here, we provide an overview of the various strategies practiced to produce EV-based hybrid systems and elucidate those advantageous features obtained by synthetic drug delivery systems upon hybridization with EVs.
Highlights
Gold nanoparticles first coated with branched PEI (AuBPEI Synthetic nanoparticles (sNPs)) and coated with Extracellular vesicles (EVs) isolated from cancer cells showed significantly lower uptake by macrophages in comparison to AuBPEI sNPs without coating [48]. This evidence indicates that sNPs can inherit the immune privileged properties from EVs upon hybridization, which are possibly mediated by the demonstrated capability of EV-based hybrid systems to competitively interact with SIRPα present on macrophages [46]
The acute depletion of cholesterol, which is crucial for lipid raft formation in cell membranes, led to an impaired uptake of SKOV3-derived EVs hybridized with polyplexes but not of the polyplexes alone, suggesting that the addition of EV surface features can alter sNP internalization mechanisms [34]
drug delivery systems (DDS) due to the reported improvements obtained upon hybridization with EVs, including greater colloidal stability, enhanced cargo delivery and targeting profiles, and immunoevasive properties
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The molecular structure of the sNP surface as well as their particle size and shape determine properties such as sNP stability and solubility [3] These properties can be customized by modifying the sNP chemistry, allowing the production of an extensive variety of formulations for drug delivery applications. EVs produced upon the fusion of multivesicular endosomes with the plasma membrane or formed by budding of the cell membrane can be isolated endosomes with the membrane or formed by budding the cell membrane be isolated and hybridized withplasma synthetic nanoparticles (e.g., synthetic ofpolymeric or lipidiccan nanoparticles and hybridized with synthetic nanoparticles (e.g., synthetic polymeric or lipidic nanoparticles loaded loaded with a therapeutic cargo) through different production strategies in order to develop. With therapeutic cargo) through different production in order develop EV-based hybrid systems capable of delivering the cargo into recipient cells (yellow).
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