Research ArticleNanomedicine

Radiation therapy primes tumors for nanotherapeutic delivery via macrophage-mediated vascular bursts

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Science Translational Medicine  31 May 2017:
Vol. 9, Issue 392, eaal0225
DOI: 10.1126/scitranslmed.aal0225

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Culling cancer by vacating the vasculature

Although it is important for blood vessels to maintain barrier function under most conditions, in cancer therapy, vascular permeability enhances drug delivery to tumors. Miller et al. used intravital microscopy and computational modeling to show that a single, low dose of radiation therapy could induce transient, dynamic, and localized vascular “bursting”—increased permeability, coinciding with extravasation of fluid, cells, and nanoparticles from blood vessels in tumors. Along with vascular bursting, radiation enlarged blood vessel volume and the number of tumor-associated macrophages in mouse xenografts and patient tumor biopsies. These tumor-associated macrophages took up drug-laden nanoparticles, inducing greater drug delivery to tumors. This study demonstrates an alternative strategy for improving targeted nanotherapy delivery by modifying the local tumor microenvironment rather than the nanoparticle itself.

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