Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency.
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 e...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0214545 |
| _version_ | 1818925479569129472 |
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| author | Christina Schindler Andie Collinson Carl Matthews Amy Pointon Lesley Jenkinson Ralph R Minter Tristan J Vaughan Natalie J Tigue |
| author_facet | Christina Schindler Andie Collinson Carl Matthews Amy Pointon Lesley Jenkinson Ralph R Minter Tristan J Vaughan Natalie J Tigue |
| author_sort | Christina Schindler |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:41:53Z |
| format | Article |
| id | doaj.art-d2a3717382b14d8298b565839ea17c6b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:41:53Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d2a3717382b14d8298b565839ea17c6b2022-12-21T19:56:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021454510.1371/journal.pone.0214545Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency.Christina SchindlerAndie CollinsonCarl MatthewsAmy PointonLesley JenkinsonRalph R MinterTristan J VaughanNatalie J TigueDoxorubicin 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.https://doi.org/10.1371/journal.pone.0214545 |
| spellingShingle | Christina Schindler Andie Collinson Carl Matthews Amy Pointon Lesley Jenkinson Ralph R Minter Tristan J Vaughan Natalie J Tigue Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency. PLoS ONE |
| title | Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency. |
| title_full | Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency. |
| title_fullStr | Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency. |
| title_full_unstemmed | Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency. |
| title_short | Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency. |
| title_sort | exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency |
| url | https://doi.org/10.1371/journal.pone.0214545 |
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