Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs

肿瘤细胞衍生的外泌体可以回到其来源细胞,并可用作运送抗癌药物的特洛伊木马

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作者:Li Qiao, Shiqi Hu, Ke Huang, Teng Su, Zhenhua Li, Adam Vandergriff, Jhon Cores, Phuong-Uyen Dinh, Tyler Allen, Deliang Shen, Hongxia Liang, Yongjun Li, Ke Cheng

Conclusion

Here we demonstrate that the exosomes' ability to target the parent cancer is a phenomenon that opens up new ways to devise targeted therapies to deliver anti-tumor drugs.

Methods

We isolated exosomes from two cancer cell lines, then co-cultured each type of cancer cells with these two kinds of exosomes and quantified exosome. HT1080 or Hela exosomes were systemically injected to Nude mice bearing a subcutaneous HT1080 tumor to investigate their cancer-homing behavior. Moreover, cancer cell-derived exosomes were engineered to carry Doxil (a common chemotherapy drug), known as D-exo, were used to detect their target and therapeutic efficacy as anti-cancer drugs. Exosome proteome array analysis were used to reveal the mechanism underly this phenomenon.

Results

Exosomes derived from cancer cells fuse preferentially with their parent cancer cells, in vitro. Systemically injected tumor-derived exosomes home to their original tumor tissues. Moreover, compared to Doxil alone, the drug-loaded exosomes showed enhanced therapeutic retention in tumor tissues and eradicated them more effectively in nude mice. Exosome proteome array analysis revealed distinct integrin expression patterns, which might shed light on the underlying mechanisms that explain the exosomal cancer-homing behavior.

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