Format

Send to

Choose Destination
Biochim Biophys Acta. 2014 Nov;1838(11):2954-65. doi: 10.1016/j.bbamem.2014.07.026. Epub 2014 Aug 4.

Examination of the specificity of tumor cell derived exosomes with tumor cells in vitro.

Author information

1
University of Colorado Denver, Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. Electronic address: Tyson.Smyth@ucdenver.edu.
2
University of Colorado Denver, Anschutz Medical Campus, Department of Neurosurgery, Aurora, CO, USA.
3
University of Colorado Denver, Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. Electronic address: Tom.Anchordoquy@ucdenver.edu.

Abstract

Small endogenous vesicles called exosomes are beginning to be explored as drug delivery vehicles. The in vivo targets of exosomes are poorly understood; however, they are believed to be important in cell-to-cell communication and may play a prominent role in cancer metastasis. We aimed to elucidate whether cancer derived exosomes can be used as drug delivery vehicles that innately target tumors over normal tissue. Our in vitro results suggest that while there is some specificity towards cancer cells over "immortalized" cells, it is unclear if the difference is sufficient to achieve precise in vivo targeting. Additionally, we found that exosomes associate with their cellular targets to a significantly greater extent (>10-fold) than liposomes of a similar size. Studies on the association of liposomes mimicking the unique lipid content of exosomes revealed that the lipid composition contributes significantly to cellular adherence/internalization. Cleavage of exosome surface proteins yielded exosomes exhibiting reduced association with their cellular targets, demonstrating the importance of proteins in binding/internalization. Furthermore, although acidic conditions are known to augment the metastatic potential of tumors, we found that cells cultured at low pH released exosomes with significantly less potential for cellular association than cells cultured at physiological pH.

KEYWORDS:

Association; Exosomes; Liposomes; Protein cleavage; pH

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center