Amplification of Anticancer Efficacy by Co-delivery of Doxorubicin and Lonidamine with Extracellular Vesicles

Overview

Journal Drug Deliv

Specialty Pharmacology

Date 2022 Jan 5

PMID 34984953

Citations 17

Authors

Huizhen Li

Wan Xu

Fang Li

Ru Zeng

Xiuming Zhang

Xianwu Wang

Shaojun Zhao

Jian Weng

Zhu Li

Liping Sun

Affiliations

Soon will be listed here.

Abstract

Chemotherapy is commonly used for the treatment of lung cancer, but strong side effects and low treatment efficacy limit its clinical application. Here, extracellular vesicles (EVs) as natural drug delivery carriers were used to load conventional anticancer drug doxorubicin (DOX) and a chemosensitizer lonidamine (LND). Two types of EVs with different sizes (16k EVs and 120k EVs) were prepared using different centrifugation forces. We found that co-delivery of DOX and LND with both EVs enhanced the cytotoxicity and reduced the dose of the anticancer drug significantly . Effective delivery of anti-cancer drugs to cancer cells was achieved by direct fusion of EVs with the plasma membrane of cancer cells. On the other hand, DOX and LND inhibited cancer cell proliferation by increasing DNA damage, suppressing ATP production, and accelerating ROS generation synergistically. DOX and LND loaded EVs were also applied to the mouse lung cancer model and exhibited significant anticancer activity. study showed that smaller EVs exhibited higher anticancer efficiency. In conclusion, the co-delivery of the anticancer drug and the chemosensitizer with EVs may have potential clinical applications for cancer therapy.

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