Extracellular Vesicle-Based Hybrid Systems for Advanced Drug Delivery

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.

Engineered Cancer-Derived Small Extracellular Vesicle-Liposome Hybrid Delivery System for Targeted Treatment of Breast Cancer

“…Liposomes and sEVs have been reported to fuse by various techniques such as incubation, extrusion, sonication, and freeze–thaw methods. ,, Many fusion techniques have low fusion efficiency with alternations of membrane structure or damage of the membrane proteins . Thus, there is a need for a membrane fusion method that does not compromise the integrity of hybrid particles.…”

“…Considering the advantages and disadvantages of liposomes and sEVs, an emerging advanced hybrid particle delivery platform combining the beneficial properties of both liposomes and sEVs in a single carrier has been facilitated in recent years. , The hybrid delivery system has the superiority of sEVs regarding improved circulation, limited immunogenicity, and targeted accumulation and also benefits from the liposome field with easier surface functionalization, higher production yield, and drug loading capacity. , In 2016, Sato et al first prepared hybrid particles by fusing sEVs from murine macrophage cells (Raw 264.7) with liposomes using the freeze–thaw method . After that, the sEV-liposome hybrid particle system has attracted significant attention from researchers in the drug delivery field, and intensive studies have been conducted to explore its ability as an advanced delivery platform .…”

Liposomes or Extracellular Vesicles: A Comprehensive Comparison of Both Lipid Bilayer Vesicles for Pulmonary Drug Delivery

“…However, LPs still have safety and stability issues, such as mononuclear phagocytic system (MPS) clearance, toxicity at high doses, and host immune reactions upon frequent administration [ 243 ]. LPs limitations can be overcome by EVs, which have recently been investigated as a promising drug delivery system [ 244 ]. Being naturally occurring lipid-based molecular carriers, EVs show good safety profiles and lower stability issues, as well as do not cause cell death and inflammation upon repeated administration due to their biocompatibility and low immunogenicity [ 245 ].…”

Therapeutic Strategy of Mesenchymal-Stem-Cell-Derived Extracellular Vesicles as Regenerative Medicine

“…Extracellular vesicles (EVs), which are nano- to micro-sized lipid bilayer membrane particles secreted by host cells, play critical roles in novel intercellular communication mechanisms, mediating the transduction of functional molecules with physiological activity, such as microRNAs, mRNAs, proteins, and lipids ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ,…”