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Engineering tumoral vascular leakiness with gold nanoparticles

Author

Listed:
  • Magdiel Inggrid Setyawati

    (National University of Singapore, Department of Chemical and Biomolecular Engineering
    Nanyang Technological University, School of Materials Science and 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)
    The University of Tokyo)

  • 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)

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.

Suggested Citation

  • Magdiel Inggrid Setyawati & Qin Wang & Nengyi Ni & Jie Kai Tee & Katsuhiko Ariga & Pu Chun Ke & Han Kiat Ho & Yucai Wang & David Tai Leong, 2023. "Engineering tumoral vascular leakiness with gold nanoparticles," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40015-4
    DOI: 10.1038/s41467-023-40015-4
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    References listed on IDEAS

    as
    1. M.I. Setyawati & C.Y. Tay & S.L. Chia & S.L. Goh & W. Fang & M.J. Neo & H.C. Chong & S.M. Tan & S.C.J. Loo & K.W. Ng & J.P. Xie & C.N. Ong & N.S. Tan & D.T. Leong, 2013. "Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin," Nature Communications, Nature, vol. 4(1), pages 1-12, June.
    2. Glen DeLoid & Joel M. Cohen & Tom Darrah & Raymond Derk & Liying Rojanasakul & Georgios Pyrgiotakis & Wendel Wohlleben & Philip Demokritou, 2014. "Estimating the effective density of engineered nanomaterials for in vitro dosimetry," Nature Communications, Nature, vol. 5(1), pages 1-10, May.
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    Cited by:

    1. Shuangshuang Wan & Kepeng Wang & Peihong Huang & Xian Guo & Wurui Liu & Yaocheng Li & Jingjing Zhang & Zhiyang Li & Jiacheng Song & Wenjing Yang & Xianzheng Zhang & Xianguang Ding & David Tai Leong & , 2024. "Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Yuhuan Li & Nengyi Ni & Myeongsang Lee & Wei Wei & Nicholas Andrikopoulos & Aleksandr Kakinen & Thomas P. Davis & Yang Song & Feng Ding & David Tai Leong & Pu Chun Ke, 2024. "Endothelial leakiness elicited by amyloid protein aggregation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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