Nanoparticles promote in vivo breast cancer cell intravasation and extravasation by inducing endothelial leakiness

While most cancer nanomedicine is designed to eliminate cancer, the nanomaterial per se can lead to the formation of micrometre-sized gaps in the blood vessel endothelial walls. Nanomaterials-induced endothelial leakiness (NanoEL) might favour intravasation of surviving cancer cells into the surroun...

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Bibliographic Details
Published in:Nature nanotechnology Vol. 14; no. 3; pp. 279 - 286
Main Authors: Peng, Fei, Setyawati, Magdiel Inggrid, Tee, Jie Kai, Ding, Xianguang, Wang, Jinping, Nga, Min En, Ho, Han Kiat, Leong, David Tai
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.03.2019
Subjects:
Animal models
Animals
Blood vessels
Blood Vessels - pathology
Breast cancer
Breast Neoplasms - pathology
Cadherins
Cancer
Cell Line, Tumor
Disruption
Endothelial Cells - pathology
Extravasation
Extravasation of Diagnostic and Therapeutic Materials - pathology
Female
Gold
Humans
Metal Nanoparticles - chemistry
Metastases
Metastasis
Mice
Nanomaterials
Nanoparticles
Nanotechnology
Neoplasm Metastasis
Neoplastic Cells, Circulating - pathology
Permeability
Silica
Silicon dioxide
Titanium - chemistry
Titanium dioxide
ISSN:1748-3387, 1748-3395, 1748-3395
Online Access:Get full text
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Summary:While most cancer nanomedicine is designed to eliminate cancer, the nanomaterial per se can lead to the formation of micrometre-sized gaps in the blood vessel endothelial walls. Nanomaterials-induced endothelial leakiness (NanoEL) might favour intravasation of surviving cancer cells into the surrounding vasculature and subsequently extravasation, accelerating metastasis. Here, we show that nanoparticles induce endothelial leakiness through disruption of the VE-cadherin-VE-cadherin homophilic interactions at the adherens junction. We show that intravenously injected titanium dioxide, silica and gold nanoparticles significantly accelerate both intravasation and extravasation of breast cancer cells in animal models, increasing the extent of existing metastasis and promoting the appearance of new metastatic sites. Our results add to the understanding of the behaviour of nanoparticles in complex biological systems. The potential for NanoEL needs to be taken into consideration when designing future nanomedicines, especially nanomedicine to treat cancer.
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ISSN:1748-3387
1748-3395
1748-3395
DOI:10.1038/s41565-018-0356-z