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IMMUNOENGINEERING

Cutting ties

Nature Reviews Materials volume 4, page 354 (2019)Cite this article

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The formation of new blood vessels is a major cause of tumour regrowth after chemotherapy. Neoangiogenesis is facilitated by macrophages, recruited to the tumour site during treatment, and by endothelial cells in the tumour microenvironment, which both bind angiopoietin — a vascular growth factor. Now, writing in ACS Nano, Guangjun Nie, Ying Zhao, Zhihai Qin and colleagues report a peptide nanoparticle that binds to the angiopoietin receptor on macrophages and endothelial cells and inhibits tumour blood vessel formation. Treatment with the nanoparticles in combination with chemotherapy prevents cancer relapse and metastasis in a triple-negative breast cancer mouse model.

To address these limitations, the researchers designed a dual-responsive amphiphilic peptide that self-assembles into nanoparticles at physiological pH. The peptide contains the T4 sequence, a cleavage site for legumain, which is a protease overexpressed in tumour cells, a hydrophilic sequence to prolong the blood circulation time and the hydrophobic molecule diethylaminopropyl isothiocyanate (DEAP). DEAP is protonated at pH 6.7–7.1, which is the characteristic pH range of a tumour microenvironment. Protonation of DEAP leads to swelling of the nanoparticles and thus exposure of the protease cleavage site. Enzymatic processing then causes the release of the T4 peptide.

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  1. Nature Reviews Materials http://www.nature.com/natrevmats/

    Christine-Maria Horejs

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  1. Christine-Maria Horejs
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Correspondence to Christine-Maria Horejs.

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Horejs, CM. Cutting ties. Nat Rev Mater 4, 354 (2019). https://doi.org/10.1038/s41578-019-0117-0

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