Exosomes: cell-created drug delivery systems

Familtseva, Anastasia; Jeremić, Nevena; Tyagi, Suresh C.

doi:10.1007/s11010-019-03545-4

Cited by 133 publications

(92 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability of EVs to package and transport a variety of biological cargos has prompted investigators to examine the possibility of loading EVs with specific therapeutic content [107]. Several methods of EV loading have been developed, including electroporation, transfection, and incubation, among others [108]. Utilizing one of these methods, it is conceivable that EVs may be loaded with CYP enzyme, along with CPR.…”

Section: Targeted Delivery Of Ev Cyps For Prodrug Activationmentioning

confidence: 99%

Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell–Cell Interactions

Gerth

Kumar

Mahon

et al. 2019

IJMS

View full text Add to dashboard Cite

The cytochrome P450 (CYP) family of enzymes is known to metabolize the majority of xenobiotics. Hepatocytes, powerhouses of CYP enzymes, are where most drugs are metabolized into non-toxic metabolites. Additional tissues/cells such as gut, kidneys, lungs, blood, and brain cells express selective CYP enzymes. Extrahepatic CYP enzymes, especially in kidneys, also metabolize drugs into excretable forms. However, extrahepatic cells express a much lower level of CYPs than hepatocytes. It is possible that the liver secretes CYP enzymes, which circulate via plasma and are eventually delivered to extrahepatic cells (e.g., brain cells). CYP circulation likely occurs via extracellular vesicles (EVs), which carry important biomolecules for delivery to distant cells. Recent studies have revealed an abundance of several CYPs in plasma EVs and other cell-derived EVs, and have demonstrated the role of CYP-containing EVs in xenobiotic-induced toxicity via cell–cell interactions. Thus, it is important to study the mechanism for packaging CYP into EVs, their circulation via plasma, and their role in extrahepatic cells. Future studies could help to find novel EV biomarkers and help to utilize EVs in novel interventions via CYP-containing EV drug delivery. This review mainly covers the abundance of CYPs in plasma EVs and EVs derived from CYP-expressing cells, as well as the potential role of EV CYPs in cell–cell communication and their application with respect to novel biomarkers and therapeutic interventions.

show abstract

Section: Targeted Delivery Of Ev Cyps For Prodrug Activationmentioning

confidence: 99%

Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell–Cell Interactions

Gerth

Kumar

Mahon

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…In particular, engineering specific targeting molecules on the exosomal surface can facilitate their accumulation at desired sites of diseased tissues in vivo . Thus, the biocompatibility, low toxicity profiles, and possibly allogenic property of exosomes support their application in drug delivery 42.…”

Section: Discussionmentioning

confidence: 96%

Extracellular vesicles expressing a single-chain variable fragment of an HIV-1 specific antibody selectively target Env⁺ tissues

et al. 2019

View full text Add to dashboard Cite

Rationale: Antiretroviral therapy can effectively suppress HIV-1 replication in the peripheral blood to an undetectable level. However, elimination of the latent virus in reservoirs remains a challenge and is a major obstacle in the treatment of HIV-1-infected patients. Exosomes exhibit huge promise as an endogenous drug delivery nanosystem for delivering drugs to solid tissues given their unique properties, including low immunogenicity, innate stability, high delivery efficiency, and most importantly the ability to penetrate solid tissues due to their lipophilic properties.Methods: We engineered and expressed the scFv of a high affinity HIV-1-specific monoclonal antibody, 10E8, on the exosomal surface (10E8scFv-exos). Subsequently, the 10E8scFv-exos were loaded with curcumin (Cur), a chemical that kills HIV-1-infected cells, or miR-143, an apoptosis-inducing miRNA. We tested the ability of 10E8scFv-exos to deliver cargo to Env+ target cells and tissues, as well as their ability to suppress HIV-1 infection.Results: 10E8scFv-exos efficiently targeted CHO cells expressing a trimeric gp140 on their surface (Env+ cells) in vitro, as demonstrated by confocal imaging and flow cytometry. 10E8scFv-exos loaded with Cur or miR-143 showed specific killing of Env+ cells. In addition, 10E8scFv-exos loaded with Cur or miR-143 could suppress p24 expression in an HIV-1 latency cell line ACH2 and in PBMCs from an ART-treated HIV-1-infected patient. In an NCG mouse model grafted with tumorigenic Env+ CHO cells and which had developed solid tissue tumors, intravenously injected 10E8scFv-exos targeted the Env-expressing tissues and delivered Cur to induce a strong suppression of the Env+ tumor growth with low toxicity.Conclusion: In principle, engineered exosomes can deliver anti-HIV agents to solid tissues by specifically targeting cells expressing viral envelop proteins and inducing cell killing, suggesting that such an approach could be developed for eradicating virus-infected cells in tissue reservoirs.

show abstract

“…After being packaged into EVs, the cargos can be secreted and collected in an EV-carrying manner for therapeutic use [17]. The non-cell-based loading approach involves directly loading chemical or biomolecules into isolated EVs through electroporation, sonication, incubation, and/or transfection [18]. In the following content, these methods are reviewed according to the cargos.…”

Section: Ev Loading Methodsmentioning

confidence: 99%

Overview and Update on Methods for Cargo Loading into Extracellular Vesicles

et al. 2021

View full text Add to dashboard Cite

The enormous library of pharmaceutical compounds presents endless research avenues. However, several factors limit the therapeutic potential of these drugs, such as drug resistance, stability, off-target toxicity, and inadequate delivery to the site of action. Extracellular vesicles (EVs) are lipid bilayer-delimited particles and are naturally released from cells. Growing evidence shows that EVs have great potential to serve as effective drug carriers. Since EVs can not only transfer biological information, but also effectively deliver hydrophobic drugs into cells, the application of EVs as a novel drug delivery system has attracted considerable scientific interest. Recently, EVs loaded with siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, or therapeutic drugs show improved delivery efficiency and drug effect. In this review, we summarize the methods used for the cargo loading into EVs, including siRNA, miRNA, mRNA, CRISPR/Cas9, proteins, and therapeutic drugs. Furthermore, we also include the recent advance in engineered EVs for drug delivery. Finally, both advantages and challenges of EVs as a new drug delivery system are discussed. Here, we encourage researchers to further develop convenient and reliable loading methods for the potential clinical applications of EVs as drug carriers in the future.

show abstract

Exosomes: cell-created drug delivery systems

Cited by 133 publications

References 41 publications

Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell–Cell Interactions

Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell–Cell Interactions

Extracellular vesicles expressing a single-chain variable fragment of an HIV-1 specific antibody selectively target Env⁺ tissues

Overview and Update on Methods for Cargo Loading into Extracellular Vesicles

Contact Info

Product

Resources

About

Exosomes: cell-created drug delivery systems

Cited by 133 publications

References 41 publications

Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell–Cell Interactions

Circulating Extracellular Vesicles Containing Xenobiotic Metabolizing CYP Enzymes and Their Potential Roles in Extrahepatic Cells Via Cell–Cell Interactions

Extracellular vesicles expressing a single-chain variable fragment of an HIV-1 specific antibody selectively target Env+ tissues

Overview and Update on Methods for Cargo Loading into Extracellular Vesicles

Contact Info

Product

Resources

About

Extracellular vesicles expressing a single-chain variable fragment of an HIV-1 specific antibody selectively target Env⁺ tissues