Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells.

By Shin-ichiro Ohno, M. Takanashi, K. Sudo, Shinobu Ueda, A. Ishikawa, Nagahisa Matsuyama, Koji Fujita, Takayuki Mizutani, T. Ohgi, T. Ochiya and 2 more. Molecular Therapy, 2013

1,545 citations recorded by the source corpus.

Despite the therapeutic potential of nucleic acid drugs, their clinical application has been limited in part by a lack of appropriate delivery systems. Exosomes or microvesicles are small endosomally derived vesicles that are secreted by a variety of cell types and tissues. Here, we show that exosomes can efficiently deliver microRNA (miRNA) to epidermal growth factor receptor (EGFR)-expressing breast cancer cells. Targeting was achieved by engineering the donor cells to express the transmembrane domain of platelet-derived growth factor receptor fused to the GE11 peptide. Intravenously injected exosomes delivered let-7a miRNA to EGFR-expressing xenograft breast cancer tissue in RAG2-/- mice. Our results suggest that exosomes can be used therapeutically to target EGFR-expressing cancerous tissues with nucleic acid drugs.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8f22c3428825c763c51c001db5b9e798b1d72642

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Raghu Kalluri
2. E. Batrakova
3. X. Breakefield
4. M. Kim
5. Valerie S. LeBleu
6. Jiang Xia
7. Li Duan
8. Jianping Lu

In Molecular Biology

1. Raghu Kalluri
2. E. Batrakova
3. M. Kim
4. X. Breakefield
5. Valerie S. LeBleu
6. P. Vader
7. C. Théry
8. Jiang Xia

Citations in the corpus

• miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis (2020, background): “Exosomes could be used as vehicles for tumor-suppressing miRNAs which would improve the survival rates and the prognostic of cervical cancer patients [157].”
• Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting (2015, methodology): “The tumour accumulation can probably be optimised with different cell sources and target moieties; however, these data showing tumour accumulation suggests that the EVs are a viable option as a delivery modality to tumours, supporting earlier findings by others that it is feasible to harness the del”
• Advances in therapeutic applications of extracellular vesicles (2019, methodology): “Similar techniques as used for exogenous EV loading, including incubation (131) and transfection/transduction (132, 133), have been used to incorporate small RNA and small molecules endogenously into EVs via loading into producer cells.”
• Engineering exosomes for targeted drug delivery (2021, background): “In animals, GE11 exosomes loaded with the antitumor nucleic acid inhibitor miRNA let-7 significantly inhibited tumor growth, consistent with their tumor-targeting ability [59].”
• Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper (2015, background): “Other teams have reported that they were unsuccessful in using electroporation to load EVs with miRNA (140).”
• Biodistribution and Delivery Efficiency of Unmodified Tumor-Derived Exosomes (2014, result): “However, recent biodistribution studies of intravenously injected exosomes [19, 20, 22, 23], along with our own results, demonstrate the rapid clearance of exosomes by the liver and spleen.”
• Exosome Theranostics: Biology and Translational Medicine (2018, background): “Several studies have successfully modified exosomes by anchoring targeting ligands on their membrane and then introduced the exosomes to diseased cells [181, 182].”
• Quantitative and stoichiometric analysis of the microRNA content of exosomes (2014, background): “Studies delivering purified exosomes to recipient cells have reported transfer of miRNAs in experimental settings (10–12), and the use of exosomes as small RNA delivery vehicles is being studied as a potential therapeutic strategy (13, 14).”
• Using exosomes, naturally-equipped nanocarriers, for drug delivery (2015, methodology): “The same method was used to load exosomes with miRNA to epidermal growth factor receptor (EGFR)-expressing breast cancer cells [100].”