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Nanoscale Liquid Biopsy Technique Reveals More About Cancer

Ovarian tumor microenvironment (mouse model)

Something intriguing occurs when nanoparticles come into contact with biological fluids: proteins attach themselves to the nanoparticle surfaces, forming what is called a "protein corona." This phenomenon has now resulted in a technique that could allow doctors and researchers to glean additional information from the blood of cancer patients.

When researchers from the University of Manchester extracted injected liposomes—lipid-based nanoparticles used for drug delivery with minimal side effects—from women with ovarian carcinoma receiving treatment with the chemotherapy agent liposomal doxorubicin, they found a protein corona formed in the human circulatory system that has not previously been reported "in vivo," in living beings. Prior to this point, the protein corona had only been seen "ex vivo"—outside of living beings—after the nanoparticles were dipped in blood samples. As had been the case in previous investigations involving mice, the human in vivo corona was molecularly richer than its counterpart ex vivo corona.

"We're astonished at how rich the information was on the surface of the liposomes taken from the blood," commented Kostas Kostarelos, PhD, Chair of Nanomedicine at the University of Manchester's Faculty of Medical and Human Sciences and senior author of the study, which was published in Advanced Materials.

The liposomes "captured" low-molecular-weight, low-abundance plasma proteins that conventional plasma proteomic analysis methods would be unable to detect.

"The blood is a potential goldmine of information, but there's a challenge to amplify cancer signals that would otherwise be buried within the noise," commented the study's lead author, Marilena Hadjidemetriou, PhD, who completed this study as a doctoral student at the University of Manchester. "More abundant proteins mask rarer and smaller molecules that could be significant in helping us to understand disease progression or finding potential new drug targets. This technique overcomes this challenge."

Dr. Kostarelos emphasized the broad applicability of the new biopsy method: "We hope this technique could be a springboard for further research, from monitoring disease progression or recurrence to identifying which treatment is best for each patient and potentially finding new biomarkers for early diagnosis."

For More Information

Hadjidemetriou M, McAdam S, Garner G, et al (2018). The human in vivo biomolecule corona onto PEGylated liposomes: a proof‐of‐concept clinical study. Adv Mater. [Epub ahead of print] DOI:10.1002/adma.201803335

​Image credit: Chris Booth, Kyle Cowdrick, and Frank C. Marini. Courtesy of the National Cancer Institute / Comprehensive Cancer Center of Wake Forest University.

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