Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Al-Jipouri, Ali; Eritja, Àuria; Bozic, Milica

doi:10.3390/ijms25010485

Cited by 5 publications

(5 citation statements)

References 560 publications

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“…To optimize drug delivery, it is necessary to modify EV cargo or surface molecules [ 38 ]. Several studies have investigated various methods of cargo modification to exploit EVs as a drug delivery system [ 39 , 40 , 41 ]. The two main strategies are the indirect modification of the EV cargo via manipulation of the donor cells, and direct interventions on purified EVs.…”

Section: Ev Loading Methodsmentioning

confidence: 99%

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

Gai,

Pomatto,

Deregibus

et al. 2024

Vaccines

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Nucleic acid delivery through extracellular vesicles (EVs) is a well-preserved evolutionary mechanism in all life kingdoms including eukaryotes, prokaryotes, and plants. EVs naturally allow horizontal transfer of native as well as exogenous functional mRNAs, which once incorporated in EVs are protected from enzymatic degradation. This observation has prompted researchers to investigate whether EVs from different sources, including plants, could be used for vaccine delivery. Several studies using human or bacterial EVs expressing mRNA or recombinant SARS-CoV-2 proteins showed induction of a humoral and cell mediated immune response. Moreover, EV-based vaccines presenting the natural configuration of viral antigens have demonstrated advantages in conferring long-lasting immunization and lower toxicity than synthetic nanoparticles. Edible plant-derived EVs were shown to be an alternative to human EVs for vaccine delivery, especially via oral administration. EVs obtained from orange juice (oEVs) loaded with SARS-CoV-2 mRNAs protected their cargo from enzymatic degradation, were stable at room temperature for one year, and were able to trigger a SARS-CoV-2 immune response in mice. Lyophilized oEVs containing the S1 mRNA administered to rats via gavage induced a specific humoral immune response with generation of blocking antibodies, including IgA and Th1 lymphocyte activation. In conclusion, mRNA-containing oEVs could be used for developing new oral vaccines due to optimal mucosal absorption, resistance to stress conditions, and ability to stimulate a humoral and cellular immune response.

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Section: Ev Loading Methodsmentioning

confidence: 99%

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

Gai,

Pomatto,

Deregibus

et al. 2024

Vaccines

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show abstract

“…Extracellular vesicles (EVs) are highlighted as potential novel targets and platforms for therapeutic intervention and/or drug delivery. It is necessary to investigate their biogenesis, biodistribution, metabolism, extraction, and safety and their roles in different organs [73]. EVs contain proteins, nucleic acids, and lipids, and act as messengers for cell-to-cell communication and signaling, particularly between immune cells.…”

Section: Future Directions In Therapy 71 Nanotechnology As a New Ther...mentioning

confidence: 99%

“…Different nonclinical trials have aimed to provide comprehensive data on the pharmacokinetics and toxicity of EV products. Moreover, EVs have physiological roles in different organs and crucial pathological roles in the development of several diseases [73]. Therefore, EVs are a new powerful therapeutic option for various diseases, providing a potential therapeutic target and, as mentioned, a platform for therapeutic interventions and/or delivery [77].…”

Section: Future Directions In Therapy 71 Nanotechnology As a New Ther...mentioning

confidence: 99%

“…Moreover, LPs have a significant advantage in the context of drug delivery. Additionally, EVs have shown great potential for integrating many small molecules for therapeutic and diagnostic applications [73]. EVs can carry matrix-remodeling enzymes such as metalloproteinases as well as their regulators, contributing to modifications of the extracellular matrix (ECM) [72,78].…”

Section: Future Directions In Therapy 71 Nanotechnology As a New Ther...mentioning

confidence: 99%

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Understanding the Pathophysiology of Preeclampsia: Exploring the Role of Antiphospholipid Antibodies and Future Directions

Mitranovici,

Chiorean,

Moraru

et al. 2024

JCM

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Preeclampsia (PE) is a hypertensive disorder in pregnancy associated with significant fetal and maternal complications. Antiphospholipid syndrome (APS) is an acquired form of thrombophilia characterized by recurrent venous or arterial thrombosis and obstetric complications that significantly increases morbidity and mortality rates. While preeclampsia may not be the most prevalent obstetric complication in APS, it significantly impacts the long-term health of both mother and child. The treatment of preeclampsia in antiphospholipid syndrome is different from the treatment of preeclampsia as an independent disease. Despite current treatments involving anticoagulants, antiplatelet agents, and antihypertensive drugs, obstetric complications may persist, underscoring the need for cohesive management and effective treatments. The objective of our review is to briefly present knowledge about the physiopathology of preeclampsia and the role of antiphospholipid antibodies in this process. Based on the existing literature, our review aims to identify future directions in molecular pathology toward the discovery of biomarkers and targeted treatments. The application of multidisciplinary approaches and prognostic models, including new biomarkers, could be beneficial in the prediction of PE.

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“…There are two different methods that have been proposed for loading EVs with drugs, nucleic acids, or other cargo. The main strategies are either manipulating the cells that make the EVs or directly modifying purified EVs [ 48 , 49 , 50 , 51 ].…”

Section: Extracellular Vesicles As Carriers Of Mrna Vaccinesmentioning

confidence: 99%

mRNA Technology and Mucosal Immunization

Toniolo,

Maccari,

Camussi

2024

Vaccines

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Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5′cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases.

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Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Cited by 5 publications

References 560 publications

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

Edible Plant-Derived Extracellular Vesicles for Oral mRNA Vaccine Delivery

Understanding the Pathophysiology of Preeclampsia: Exploring the Role of Antiphospholipid Antibodies and Future Directions

mRNA Technology and Mucosal Immunization

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