Amplification of anticancer efficacy by co-delivery of doxorubicin and lonidamine with extracellular vesicles

• Published in: Drug delivery Vol. 29; no. 1; pp. 192 - 202
• Main Authors: Li, Huizhen, Xu, Wan, Li, Fang, Zeng, Ru, Zhang, Xiuming, Wang, Xianwu, Zhao, Shaojun, Weng, Jian, Li, Zhu, Sun, Liping
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: A549 Cells; Adenosine Triphosphate - metabolism; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biocompatibility; Biomedical engineering; Biomedical materials; Cancer therapies; cancer therapy; Cell culture; Cell growth; Cell Proliferation - drug effects; Chemotherapy; Cytotoxicity; DNA damage; DNA Damage - drug effects; Dose-Response Relationship, Drug; doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Combinations; Drug dosages; Drug resistance; Engineering; Extracellular vesicles; Extracellular Vesicles - chemistry; Female; Humans; Indazoles - administration & dosage; Indazoles - pharmacology; Laboratories; lonidamine; Lung cancer; Mice; Mice, Inbred BALB C; Mice, Nude; Nanomaterials; Natural resources; Oceanography; Particle Size; Permeability; Random Allocation; Xenograft Model Antitumor Assays; lung cancer; Extracellular vesicles; lonidamine; cancer therapy; doxorubicin
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2021.2023697

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 in vitro. 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. In vivo 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.