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

Fei Peng ¹, Magdiel Inggrid Setyawati ¹, Jie Kai Tee ¹, Xianguang Ding ¹, Jinping Wang ¹, Min En Nga ², Han Kiat Ho ³, David Tai Leong ⁴

Affiliations

¹ Department of Chemical and Biomolecular Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore.
² Department of Pathology, National University Hospital and National University of Singapore, Singapore, Singapore.
³ Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore. phahohk@nus.edu.sg.
⁴ Department of Chemical and Biomolecular Engineering, Faculty of Engineering, National University of Singapore, Singapore, Singapore. cheltwd@nus.edu.sg.

PMID: 30692675
31 citations

Abstract

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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