Engineering tumoral vascular leakiness with gold nanoparticles

Magdiel Inggrid Setyawati (), Qin Wang, Nengyi Ni, Jie Kai Tee, Katsuhiko Ariga, Pu Chun Ke, Han Kiat Ho, Yucai Wang () and David Tai Leong ()
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Magdiel Inggrid Setyawati: National University of Singapore, Department of Chemical and Biomolecular Engineering
Qin Wang: The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Nengyi Ni: National University of Singapore, Department of Chemical and Biomolecular Engineering
Jie Kai Tee: National University of Singapore, Department of Pharmacy
Katsuhiko Ariga: National Institute for Materials Science (NIMS)
Pu Chun Ke: Monash University
Han Kiat Ho: National University of Singapore, Department of Pharmacy
Yucai Wang: The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
David Tai Leong: National University of Singapore, Department of Chemical and Biomolecular Engineering

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Delivering cancer therapeutics to tumors necessitates their escape from the surrounding blood vessels. Tumor vasculatures are not always sufficiently leaky. Herein, we engineer therapeutically competent leakage of therapeutics from tumor vasculature with gold nanoparticles capable of inducing endothelial leakiness (NanoEL). These NanoEL gold nanoparticles activated the loss of endothelial adherens junctions without any perceivable toxicity to the endothelial cells. Microscopically, through real time live animal intravital imaging, we show that NanoEL particles induced leakiness in the tumor vessels walls and improved infiltration into the interstitial space within the tumor. In both primary tumor and secondary micrometastases animal models, we show that pretreatment of tumor vasculature with NanoEL particles before therapeutics administration could completely regress the cancer. Engineering tumoral vasculature leakiness represents a new paradigm in our approach towards increasing tumoral accessibility of anti-cancer therapeutics instead of further increasing their anti-cancer lethality.

Date: 2023
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DOI: 10.1038/s41467-023-40015-4

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