Approaches to surface engineering of extracellular vesicles.

Extracellular vesicles (EVs) are cell-derived nanoparticles that are important mediators in intercellular communication. This function makes them auspicious candidates for therapeutic and drug-delivery applications. Among EVs, mammalian cell derived EVs and outer membrane vesicles (OMVs) produced by gram-negative bacteria are the most investigated candidates for pharmaceutical applications. To further optimize their performance and to utilize their natural abilities, researchers have strived to equip EVs with new moieties on their surface while preserving the integrity of the vesicles. The aim of this review is to give a comprehensive overview of techniques that can be used to introduce these moieties to the vesicle surface. Approaches can be classified in regards to whether they take place before or after the isolation of EVs. The producing cells can be subjected to genetic manipulation or metabolic engineering to produce surface modified vesicles or EVs are engineered after their isolation by physical or chemical means. Here, the advantages and disadvantages of these processes and their applicability for the development of EVs as therapeutic agents are discussed.

Richter M ，Vader P ，Fuhrmann G 《-》

Surface functionalization strategies of extracellular vesicles.

Rayamajhi S ，Aryal S 《-》

Membrane Derived Vesicles as Biomimetic Carriers for Targeted Drug Delivery System.

Extracellular vesicles (EVs) are membrane vesicles (MVs) playing important roles in various cellular and molecular functions in cell-to-cell signaling and transmitting molecular signals to adjacent as well as distant cells. The preserved cell membrane characteristics in MVs derived from live cells, give them great potential in biological applications. EVs are nanoscale particulates secreted from living cells and play crucial roles in several important cellular functions both in physiological and pathological states. EVs are the main elements in intercellular communication in which they serve as carriers for various endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. High tissue tropism capacity that can be conveniently mediated by surface molecules, such as integrins and glycans, is a unique feature of EVs that makes them interesting candidates for targeted drug delivery systems. The cell-derived giant MVs have been exploited as vehicles for delivery of various anticancer agents and imaging probes and for implementing combinational phototherapy for targeted cancer treatment. Giant MVs can efficiently encapsulate therapeutic drugs and deliver them to target cells through the membrane fusion process to synergize photodynamic/photothermal treatment under light exposure. EVs can load diagnostic or therapeutic agents using different encapsulation or conjugation methods. Moreover, to prolong the blood circulation and enhance the targeting of the loaded agents, a variety of modification strategies can be exploited. This paper reviews the EVs-based drug delivery strategies in cancer therapy. Biological, pharmacokinetics and physicochemical characteristics, isolation techniques, engineering, and drug loading strategies of EVs are discussed. The recent preclinical and clinical progresses in applications of EVs and oncolytic virus therapy based on EVs, the clinical challenges and perspectives are discussed.

Zhang LY ，Yang X ，Wang SB ，Chen H ，Pan HY ，Hu ZM ... -  《-》

Functional Extracellular Vesicles for Regenerative Medicine.

The unique biological characteristics and promising clinical potential of extracellular vesicles (EVs) have galvanized EV applications for regenerative medicine. Recognized as important mediators of intercellular communication, naturally secreted EVs have the potential, as innate biotherapeutics, to promote tissue regeneration. Although EVs have emerged as novel therapeutic agents, challenges related to the clinical transition have led to further functionalization. In recent years, various engineering approaches such as preconditioning, drug loading, and surface modification have been developed to potentiate the therapeutic outcomes of EVs. Also, limitations of natural EVs have been addressed by the development of artificial EVs that offer advantages in terms of production yield and isolation methodologies. In this review, an updated overview of current techniques is provided for the functionalization of natural EVs and recent advances in artificial EVs, particularly in the scope of regenerative medicine.

Kim HY ，Kwon S ，Um W ，Shin S ，Kim CH ，Park JH ，Kim BS ... -  《-》

Extracellular vesicles for drug delivery.

Extracellular vesicles (EVs) are cell-derived membrane vesicles, and represent an endogenous mechanism for intercellular communication. Since the discovery that EVs are capable of functionally transferring biological information, the potential use of EVs as drug delivery vehicles has gained considerable scientific interest. EVs may have multiple advantages over currently available drug delivery vehicles, such as their ability to overcome natural barriers, their intrinsic cell targeting properties, and stability in the circulation. However, therapeutic applications of EVs as drug delivery systems have been limited due to a lack of methods for scalable EV isolation and efficient drug loading. Furthermore, in order to achieve targeted drug delivery, their intrinsic cell targeting properties should be tuned through EV engineering. Here, we review and discuss recent progress and remaining challenges in the development of EVs as drug delivery vehicles.

Vader P ，Mol EA ，Pasterkamp G ，Schiffelers RM ... -  《-》