Engineering tumoral vascular leakiness with gold nanoparticles

• Published in: Nature communications Vol. 14; no. 1; p. 4269
• Main Authors: Setyawati, Magdiel Inggrid, Wang, Qin, Ni, Nengyi, Tee, Jie Kai, Ariga, Katsuhiko, Ke, Pu Chun, Ho, Han Kiat, Wang, Yucai, Leong, David Tai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.07.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 14/34; 14/35; 14/63; 59/5; 631/67; 639/301/357; 82/1; 82/51; Adherens junctions; Animal models; Blood vessels; Cancer; Drug delivery; Endothelial cells; Gold; Humanities and Social Sciences; Lethality; Metastases; multidisciplinary; Nanoparticles; Nanotechnology; Science; Science (multidisciplinary); Toxicity; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40015-4

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. Traditional nanomedicine relies on tumor induced EPR effect for drug delivery. Here the authors show that gold nanoparticles are independently able to induce leakiness at tumor vasculature to enhance the tumor killing effect.