Editors' ChoiceCancer

Repurposing exosomes: The (magnetic) force awakens

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Science Translational Medicine  23 Mar 2016:
Vol. 8, Issue 331, pp. 331ec50
DOI: 10.1126/scitranslmed.aaf6420

Exosomes, membrane-bound vesicles that are actively secreted by cells, present new opportunities for detecting and tracking cancers. They offer advantages as possible biomarkers of cancer: high abundance (1 mL of blood contains >109 vesicles but only 1 to 10 circulating tumor cells), prolonged stability in circulation, and genetic or protein cargo reflective of the parental cell. Although these were historically considered to be cellular waste, emerging data have increased their appreciation as mediators of cellular messaging and early protagonists in the metastatic process. More recently, scientists have tapped into key exosome attributes—their nanosize and low immunogenicity—to explore their drug delivery potential.

Qi et al. developed a method that exploits the prolific release of exosomes (~100 trillion per day) from circulating reticulocytes, red blood cell precursors. The authors harnessed magnetism to bypass conventional exosome isolation methods (such as ultracentrifugation), which are laborious and cause difficulties with redispersion of the exosomes for eventual intravenous delivery. In this study, serum solution was mixed with superparamagnetic nanoparticles (SPMN) that cluster around each exosome and accumulate magnetic properties when exposed to external magnetic forces. Under moderate magnetic forces, SPMN-exosomes were effectively separated and directly purified. Using highly regulated microfluidic systems to simulate artery, vein, and capillary blood flow, the researchers noted that SPMN-exosomes were best retained under slower flow rates similar to those observed inside tumors. To capitalize on their magnetic targeting, the authors then loaded the SPMN-exosomes with chemotherapy (doxorubicin). Testing of these enhanced exosomes in murine xenograft models demonstrated passive and active homing to tumor sites and suppression of tumor growth.

This early pilot work poses some caveats. Applying external magnetic forces poses practical challenges for clinical use, yet could inspire bioengineering opportunities such as implantable intratumoral magnets or ingestible magnetic capsules. Flow rates within tumors are dynamic and influenced by prior and existing treatments such as antiangiogenic drugs. Adopting systems biology and molecular imaging principles could generate advanced in vivo models with sophisticated readouts to assess SPMN-exosome targeting in a physiological context, measure uptake with single-cell resolution, and compare performance with other nanoparticle drugs that are gaining traction. Mass production of various tumor-targeted exosomes could sustain their translational impact. The force is indeed strong.

H. Qui et al., Blood exosomes endowed with magnetic and targeting properties for cancer therapy. ACS Nano. 10.1021/acsnano.5b06939 (2016). [Abstract]

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