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 ... -  《-》

Prospects and challenges of extracellular vesicle-based drug delivery system: considering cell source.

Meng W ，He C ，Hao Y ，Wang L ，Li L ，Zhu G ... -  《-》

Recent advances on extracellular vesicles in therapeutic delivery: Challenges, solutions, and opportunities.

Extracellular vesicles (EVs) are intrinsic mediators of intercellular communication in our body, allowing functional transfer of biomolecules (lipids, proteins, and nucleic acid) between diverse locations. Such an instrumental role evokes a surge of interest within the drug delivery community in tailoring EVs for therapeutic delivery. These vesicles represent a novel generation of drug delivery systems, providing high delivery efficiency, intrinsic targeting properties, and low immunogenicity. In the recent years, considerable research efforts have been directed toward developing safe and efficient EV-based delivery vehicles. Although EVs are shown to harbor great promise in therapeutic delivery, substantial improvements in exploring standardized isolation techniques with high efficiency and robust yield, scalable production, standard procedures for EV storage, efficient loading methods without damaging EV integrity, understanding their in vivo trafficking, and developing novel EV-based nanocarriers are still required before their clinical transformation. In this review, we seek to summarize the recent advance on harnessing EVs for drug delivery with focus on state-of-the-art solutions for overcoming major challenges.

Lu M ，Xing H ，Yang Z ，Sun Y ，Yang T ，Zhao X ，Cai C ，Wang D ，Ding P ... -  《-》

The Challenges and Possibilities of Extracellular Vesicles as Therapeutic Vehicles.

Extracellular vesicles (EVs) are small lipid-enclosed particles that can carry various types of cargo, including proteins, nucleic acids and metabolites. They are known to be released by all cell types and can be taken up by other cells, leading to the transfer of the cargo they carry. As such, they represent an important type of intercellular signalling and a natural mechanism for transferring macromolecules between cells. This ability to transfer cargo could be harnessed to deliver therapeutic molecules. Indeed, a growing body of work has described the attempt by the field to utilise EVs to deliver a range of therapeutics including RNAi, CRISPR/Cas9 and chemotherapeutics, to a specific target tissue. However, there are numerous barriers associated with the use of EVs as therapeutic vehicles, including the challenge of efficiently loading therapeutics into EVs, avoiding clearance of the EVs from circulation, targeting the correct tissue type and the inefficiency of internalisation and functional delivery of the cargo. Despite these difficulties, EVs represent a tremendous therapeutic opportunity, both for the delivery of exogenous cargo, as well as the therapeutic benefit of targeting aberrant EV signalling or treating patients with natural EVs, such as those released by mesenchymal stem cells. This review describes current knowledge on the therapeutic potential of EVs and the challenges faced by the field. Many of these challenges are due to a lack of complete understanding of EV function, but further research in this area should continue to yield new solutions that will lead to the use of EVs in the clinic.

Melling GE ，Carollo E ，Conlon R ，Simpson JC ，Carter DRF ... -  《-》

Extracellular vesicles as drug delivery systems: Why and how?

Over the past decades, a multitude of synthetic drug delivery systems has been developed and introduced to the market. However, applications of such systems are limited due to inefficiency, cytotoxicity and/or immunogenicity. At the same time, the field of natural drug carrier systems has grown rapidly. One of the most prominent examples of such natural carriers are extracellular vesicles (EVs). EVs are cell-derived membranous particles which play important roles in intercellular communication. EVs possess a number of characteristics that qualify them as promising vehicles for drug delivery. In order to take advantage of these attributes, an in-depth understanding of why EVs are such unique carrier systems and how we can exploit their qualities is pivotal. Here, we review unique EV features that are relevant for drug delivery and highlight emerging strategies to make use of those features for drug loading and targeted delivery.

Elsharkasy OM ，Nordin JZ ，Hagey DW ，de Jong OG ，Schiffelers RM ，Andaloussi SE ，Vader P ... -  《-》