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PLoS One. 2019 Mar 29;14(3):e0214545. doi: 10.1371/journal.pone.0214545. eCollection 2019.

Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency.

Author information

1
Department of Antibody Discovery and Protein Engineering, MedImmune Ltd., Cambridge, United Kingdom.
2
Mechanistic Safety and ADME Sciences, Drug Safety and Metabolism, IMED Biotech Unit, AstraZeneca, Cambridge, United Kingdom.

Abstract

Doxorubicin is a chemotherapeutic agent that is commonly used to treat a broad range of cancers. However, significant cardiotoxicity, associated with prolonged exposure to doxorubicin, limits its continued therapeutic use. One strategy to prevent the uptake of doxorubicin into cardiac cells is the encapsulation of the drug to prevent non-specific uptake and also to improve the drugs' pharmacokinetic properties. Although encapsulated forms of doxorubicin limit the cardiotoxicity observed, they are not without their own liabilities as an increased amount of drug is deposited in the skin where liposomal doxorubicin can cause palmar-plantar erythrodysesthesia. Exosomes are small endogenous extracellular vesicles, that transfer bioactive material from one cell to another, and are considered attractive drug delivery vehicles due to their natural origin. In this study, we generated doxorubicin-loaded exosomes and demonstrate their rapid cellular uptake and re-distribution of doxorubicin from endosomes to the cytoplasm and nucleus resulting in enhanced potency in a number of cultured and primary cell lines when compared to free doxorubicin and liposomal formulations of doxorubicin. In contrast to other delivery methods for doxorubicin, exosomes do not accumulate in the heart, thereby providing potential for limiting the cardiac side effects and improved therapeutic index.

Conflict of interest statement

CS, AC, CM, LJ, RRM, TJV and NJT are current or former salaried employees of MedImmune Ltd (a member of the AstraZeneca Group) and have/had stock or stock options in AstraZeneca PLC, the parent company of MedImmune. AP is a current salaried employee of AstraZeneca PLC and has stock options in AstraZeneca PLC. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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