Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity

Sana Shaikh; Muhammad Younis; Shao Yingying; Tanziela Tanziela; Liudi Yuan

doi:10.1016/j.lfs.2023.121977

Bleomycin loaded exosomes enhanced antitumor therapeutic efficacy and reduced toxicity

Life Sci. 2023 Oct 1:330:121977. doi: 10.1016/j.lfs.2023.121977. Epub 2023 Jul 25.

Authors

Sana Shaikh¹, Muhammad Younis², Shao Yingying¹, Tanziela Tanziela³, Liudi Yuan⁴

Affiliations

¹ Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
² Center for Infection and Immunity, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province 519000, China; Center for Inflammation, Immunity & Infection, Georgia State University, Institute for Biomedical Sciences, Atlanta, GA, USA.
³ State Key Laboratory of Bioelectronics (Chien-Shiung Wu Lab), School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
⁴ Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Biochemistry and Molecular Biology, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China. Electronic address: yld@seu.edu.cn.

PMID: 37499934
DOI: 10.1016/j.lfs.2023.121977

Abstract

Background: Bleomycin (BLM) is a chemotherapeutic agent with potent antitumor activity against the tumor. However, lung fibrosis is the main drawback that limits BLM use. Tumor targeted, safe, efficient and natural delivery of BLM is important to increase the effectiveness and reduce the toxic side effects. Although tumor derived Exosomes (Exo), provide a potential vehicle for in vivo drug delivery due to their cell tropism. This study primarily focuses on generating a natural delivery platform for Exo loaded with BLM and testing its therapeutic efficacy against cancer.

Methods: Exosomes were isolated from cancer cells and incubated with BLM. Exo were characterized by transmission electron microscopy, western blot analysis and nanoparticle tracking analysis. We performed in vitro and in vivo analyses to evaluate the effect of Exo-BLM.

Results: Exosomes loaded with BLM are highly cancer targeting and cause the cytotoxicity of tumor cells by ROS. The fluorescence images showed that Exo-BLM accumulated in cancer cells. The results revealed that Exo-BLM induces tumor cell apoptosis by the caspase pathway. In vivo, the treatment of Exo-BLM showed targeted ability and enhanced the antitumor activity.

Conclusion: This study provides an avenue for specific BLM therapeutics with minimal side effects.

Keywords: Bleomycin; Chemotherapy; Exosomes; Targeted drug delivery; cancer.

MeSH terms

Apoptosis
Bleomycin / pharmacology
Cell Line, Tumor
Exosomes* / metabolism
Humans
Pulmonary Fibrosis* / chemically induced
Pulmonary Fibrosis* / drug therapy
Pulmonary Fibrosis* / metabolism

Substances

Bleomycin