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

dc.contributor.author

Qiao, Li

dc.contributor.author

Hu, Shiqi

dc.contributor.author

Huang, Ke

dc.contributor.author

Su, Teng

dc.contributor.author

Li, Zhenhua

dc.contributor.author

Vandergriff, Adam

dc.contributor.author

Cores, Jhon

dc.contributor.author

Dinh, Phuong-Uyen

dc.contributor.author

Allen, Tyler

dc.contributor.author

Shen, Deliang

dc.contributor.author

Liang, Hongxia

dc.contributor.author

Li, Yongjun

dc.contributor.author

Cheng, Ke

dc.date.accessioned

2022-12-03T20:15:52Z

dc.date.available

2022-12-03T20:15:52Z

dc.date.issued

2020-01

dc.date.updated

2022-12-03T20:15:49Z

dc.description.abstract

Cancer is the second leading cause of death worldwide and patients are in urgent need of therapies that can effectively target cancer with minimal off-target side effects. Exosomes are extracellular nano-shuttles that facilitate intercellular communication between cells and organs. It has been established that tumor-derived exosomes contain a similar protein and lipid composition to that of the cells that secrete them, indicating that exosomes might be uniquely employed as carriers for anti-cancer therapeutics. 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. 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.

dc.identifier

thnov10p3474

dc.identifier.issn

1838-7640

dc.identifier.issn

1838-7640

dc.identifier.uri

https://hdl.handle.net/10161/26307

dc.language

eng

dc.publisher

Ivyspring International Publisher

dc.relation.ispartof

Theranostics

dc.relation.isversionof

10.7150/thno.39434

dc.subject

Cell Line, Tumor

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Hela Cells

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Animals

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Humans

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Mice

dc.subject

Mice, Nude

dc.subject

Polyethylene Glycols

dc.subject

Doxorubicin

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Antineoplastic Agents

dc.subject

Antibiotics, Antineoplastic

dc.subject

Drug Delivery Systems

dc.subject

Exosomes

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Su, Teng|0000-0001-7888-0763

duke.contributor.orcid

Allen, Tyler|0000-0002-8729-6339

pubs.begin-page

3474

pubs.end-page

3487

pubs.issue

8

pubs.organisational-group

Duke

pubs.organisational-group

School of Medicine

pubs.organisational-group

Clinical Science Departments

pubs.organisational-group

Medicine

pubs.organisational-group

Medicine, Cardiology

pubs.publication-status

Published

pubs.volume

10

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