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Extracellular vesicles in pharmacology: Novel approaches in diagnostics and therapy.

ABSTRACT: Exosomes are nano-sized lipid vesicles that are produced by all eukaryotic cells, and they typically range in size from 30 to 150 nm. Exosomes were discovered almost 40 years ago; however, the last two decades have attracted considerable attention due to exosomes' inherent abilities to shuttle nucleic acids, lipids and proteins between cells, along with their natural affinity to exosome target cells. From a pharmaceutical perspective, exosomes are regarded as naturally produced nanoparticle drug delivery vehicles. The application of exosomes as a means of drug delivery offers critical advantages compared to other nanoparticulate drug delivery systems, such as liposomes and polymeric nanoparticles. These advantages are due to the exosomes' intrinsic features, such as low immunogenicity, biocompatibility, stability, and their ability to overcome biological barriers. Herein, we outline the structure and origin of exosomes, as well as their biological functions. We also touch upon recent advances in exosome labeling, imaging and drug loading. Finally, we discuss exosomes in targeted drug delivery and clinical trial development.

SUBMITTER: Quadri Z

PROVIDER: S-EPMC8760625 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Extracellular vesicles in pharmacology: Novel approaches in diagnostics and therapy.

Quadri Zainuddin Z Elsherbini Ahmed A Bieberich Erhard E

Pharmacological research 20211202

Exosomes are nano-sized lipid vesicles that are produced by all eukaryotic cells, and they typically range in size from 30 to 150 nm. Exosomes were discovered almost 40 years ago; however, the last two decades have attracted considerable attention due to exosomes' inherent abilities to shuttle nucleic acids, lipids and proteins between cells, along with their natural affinity to exosome target cells. From a pharmaceutical perspective, exosomes are regarded as naturally produced nanoparticle drug ...[more]

PMID: 34863822

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Project description:Extracellular vesicles (EVs) derived from the plasma of oncological patients exhibit significant tumor-targeting properties, unlike those from healthy individuals. We have previously shown the feasibility of formulating the near-infrared (NIR) fluorescent dye indocyanine green (ICG) with patient-derived extracellular vesicles (PDEVs) for selective delivery to neoplastic tissue. This staining protocol holds promise for clinical application in intraoperative tumor margin imaging, enabling precise neoplastic tissue resection. To this end, we propose the ONCOGREEN protocol, involving PDEV isolation, ICG loading, and reinfusion into the same patients. Methods: By in vivo studies on mice, we outlined key pharmacological parameters of PDEVs-ICG for intraoperative tumor imaging, PDEV biodistribution kinetics, and potential treatment-related toxicological effects. Additionally, we established a plasmapheresis-based protocol for isolating autologous PDEVs, ensuring the necessary large-scale dosage for human treatment. A potential lyophilization-based preservation method was also explored to facilitate the storage and transport of PDEVs. Results: The study identified the effective dose of PDEVs-ICG necessary for clear intraoperative tumor margin imaging. The biodistribution kinetics of PDEVs showed favorable targeting to neoplastic tissues, without off-target distribution. Toxicological assessments revealed no significant adverse effects associated with the treatment. The plasmapheresis-based isolation protocol successfully yielded a sufficient quantity of autologous PDEVs, and the lyophilization preservation method maintained the functional integrity of PDEVs for subsequent clinical application. Conclusions: Our research lays the groundwork for the direct clinical application of autologous PDEVs, initially focusing on intraoperative imaging. Utilizing autologous PDEVs has the potential to accelerate the integration of EVs as a targeted delivery tool for anti-neoplastic agents to cancerous tissue. This approach promises to enhance the precision of neoplastic tissue resection and improve overall surgical outcomes for oncological patients.

Dataset Information

Extracellular vesicles in pharmacology: Novel approaches in diagnostics and therapy.

Publications

Extracellular vesicles in pharmacology: Novel approaches in diagnostics and therapy.

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