Interest of extracellular vesicles in regards to lipid nanoparticle based systems for intracellular protein delivery

Saux, Sarah Le; Aubert-Pouëssel, Anne; Mohamed, K.E.; Martineau, Pierre; Guglielmi, Laurence; Devoisselle, Jean-Marie; Legrand, Philippe; Chopineau, Joël

doi:10.1016/j.addr.2021.113837

Cited by 27 publications

(18 citation statements)

References 141 publications

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“…Here again, a weak activity was observed in the absence of the dimerizer, suggesting that a small portion of the overexpressed cargo is passively and inefficiently loaded into EVs, in accordance with previous observations. 4,6 Remarkably, the dimerizer increased the loading of the cargo by 4-fold (Figure 2F). Importantly, fraction 7 contained classical EV markers and was depleted of a negative marker such as trans-Golgi network glycoprotein 46 (TGN46) (Figure 2G).…”

Section: ■ Resultsmentioning

confidence: 92%

“…At least two steps of the delivery process can be manipulated to potentiate the release of an EV cargo within acceptor cells. , One is the loading of the cargo into EVs and the second is the fusion between the EV membrane and the target membrane that enables EV cargo delivery.…”

Section: Introductionmentioning

confidence: 99%

“… 2 EVs can cross biological barriers such as the blood–brain barrier 3 and have a higher biocompatibility than liposomes. 4 All of these properties make EVs excellent candidates for a new generation of drug delivery systems (DDS).…”

Section: Introductionmentioning

confidence: 99%

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Virus-Free Method to Control and Enhance Extracellular Vesicle Cargo Loading and Delivery

Bui

Dancourt

Lavieu

2023

ACS Appl. Bio Mater.

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Extracellular vesicles (EVs)�including exosomes and micro-vesicles�are involved in cell−cell communication. EVs encapsulate different types of molecules such as proteins or nucleotides and are long-lasting contenders for the establishment of personalized drug delivery systems. Recent studies suggest that the intrinsic capacities for uptake and cargo delivery of basic EVs might be too limited to serve as a potent delivery system. Here, we develop two synergistic methods to, respectively, control EV cargo loading and enhance EV cargo delivery through fusion without requirement for any viral fusogenic protein. Briefly, cargo loading is enabled through a reversible drug-inducible system that triggers the interaction between a cargo of interest and CD63, a wellestablished transmembrane EV marker. Enhanced cargo delivery is promoted by overexpressing Syncytin-1, an endogenous retrovirus envelop protein with fusogenic properties encoded by the human genome. We validate our bioengineered EVs in a qualitative and quantitative manner. Finally, we utilize this method to develop highly potent killer EVs, which contain a lethal toxin responsible for protein translation arrest and acceptor cell death. These advanced methods and future downstream applications may open promising doors in the manufacture of virus-free and EV-based delivery systems.

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Section: ■ Resultsmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Virus-Free Method to Control and Enhance Extracellular Vesicle Cargo Loading and Delivery

Bui

Dancourt

Lavieu

2023

ACS Appl. Bio Mater.

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“…Combining EVs with hydrogels and liposomes is increasingly common. Compared with existing stand-alone inorganic nanocarriers such as gold nanoparticles and therapeutic nano-bioconjugates, this combinatorial drug delivery approach improves EVs targeting and drug encapsulation efficiency [ 168 – 173 ]. Furthermore, the exceptional biocompatibility of the co-loading system renders it suitable for tumor-targeted therapy.…”

Section: Engineered Evs In Tumor Therapymentioning

confidence: 99%

Application of engineered extracellular vesicles for targeted tumor therapy

et al. 2022

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All cells, including prokaryotes and eukaryotes, could release extracellular vesicles (EVs). EVs contain many cellular components, including RNA, and surface proteins, and are essential for maintaining normal intercellular communication and homeostasis of the internal environment. EVs released from different tissues and cells exhibit excellent properties and functions (e.g., targeting specificity, regulatory ability, physical durability, and immunogenicity), rendering them a potential new option for drug delivery and precision therapy. EVs have been demonstrated to transport antitumor drugs for tumor therapy; additionally, EVs' contents and surface substance can be altered to improve their therapeutic efficacy in the clinic by boosting targeting potential and drug delivery effectiveness. EVs can regulate immune system function by affecting the tumor microenvironment, thereby inhibiting tumor progression. Co-delivery systems for EVs can be utilized to further improve the drug delivery efficiency of EVs, including hydrogels and liposomes. In this review, we discuss the isolation technologies of EVs, as well as engineering approaches to their modification. Moreover, we evaluate the therapeutic potential of EVs in tumors, including engineered extracellular vesicles and EVs' co-delivery systems.

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“…They are classified into two major subcategories based on biogenesis and size under healthy conditions. Roughly described, microvesicles are 50–1000 nm in diameter and are released by budding directly from the cell plasma membrane [ 25 , 26 ]. Exosomes, the smallest EVs, are single-cell membrane vesicles with a size of approximately 30–150 nm and a density of about 1.13–1.21 g/mL, and have been extensively studied [ 17 , 25 ].…”

Section: An Overview Of the Characteristics Of Extracellular Vesiclesmentioning

confidence: 99%

The Emerging Role of Extracellular Vesicles from Mesenchymal Stem Cells and Macrophages in Pulmonary Fibrosis: Insights into miRNA Delivery

Zhang

Feng

et al. 2022

Pharmaceuticals

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Pulmonary fibrosis is a type of chronic, progressive, fibrotic lung disease of unclear cause with few treatment options. Cell therapy is emerging as a promising novel modality for facilitating lung repair. Mesenchymal stem cell (MSC)-based and macrophage-based cell therapies are regarded as promising strategies to promote lung repair, due to incredible regenerative potential and typical immunomodulatory function, respectively. Extracellular vesicles (EVs), including exosomes and microvesicles, are cell-derived lipid-bilayer membrane vesicles that are secreted from virtually every cell and are involved in intercellular communication by delivering expansive biological cargos to recipients. This review provides a deep insight into the recent research progress concerning the effects of MSC and macrophage-associated EVs on the pathogenesis of pulmonary fibrosis. In addition to discussing their respective vital roles, we summarize the importance of cross-talk, as macrophages are vital for MSCs to exert their protective effects through two major patterns, including attenuating macrophage activation and M1 phenotype macrophage polarization. Moreover, miRNAs are selectively enriched into EVs as essential components, and consideration is given to the particular effects of EV-associated miRNAs.

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Interest of extracellular vesicles in regards to lipid nanoparticle based systems for intracellular protein delivery

Cited by 27 publications

References 141 publications

Virus-Free Method to Control and Enhance Extracellular Vesicle Cargo Loading and Delivery

Virus-Free Method to Control and Enhance Extracellular Vesicle Cargo Loading and Delivery

Application of engineered extracellular vesicles for targeted tumor therapy

The Emerging Role of Extracellular Vesicles from Mesenchymal Stem Cells and Macrophages in Pulmonary Fibrosis: Insights into miRNA Delivery

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