Editors' ChoiceNanomedicine

Bad plumbing benefits nanoparticles

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Science Translational Medicine  16 Mar 2016:
Vol. 8, Issue 330, pp. 330ec46
DOI: 10.1126/scitranslmed.aaf6185

Tumor vasculature is known to be immature and leaky. Its hyperpermeability is thought to be the cause of high tumor interstitial pressure as well as the enhanced permeability and retention (EPR) effect, in which small particles escape the vasculature and are retained in the tumor. The traditional view of tumor vessel leakiness is that they possess pores and are constantly leaky. However, this view does not completely account for observations of uneven nanoparticle distribution within tumors despite their small size. Matsumoto et al. aimed to characterize and understand the differences in tumor distribution between 30- and 70-nm fluorescent nanoparticles. To visualize their distribution, the investigators used intravital microscopy in mice bearing human pancreatic and glioblastoma tumors. They observed “eruptions”—vascular bursts followed by brief, vigorous outflows of fluid—from the tumors. Both types of nanoparticles were released by these eruptions, but the smaller nanoparticles were dispersed more readily. Based on these observations, the authors proposed a “dynamic vent” model for tumor vasculature.

The results from this study have strong implications for designing drug delivery systems for cancer, suggesting that even very large particles can extravasate into the tumor interstitium. In addition, the study provides more support for the EPR effect as well as an explanation for tumor distribution variability between different sizes of nanoparticles. How best to take advantage of this dynamic vent, to design more effective nanotherapeutics for cancer treatment, is yet to be seen.

Y. Matsumoto et al., Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery. Nat. Nanotechnol. 10.1038/nnano.2015.342 (2016). [Abstract]

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