The dose threshold for nanoparticle tumour delivery

Ben Ouyang; Wilson Poon; Yi Nan Zhang; Zachary P. Lin; Benjamin R. Kingston; Anthony J. Tavares; Yuwei Zhang; Juan Chen; Michael S. Valic; Abdullah M. Syed; Presley MacMillan; Julien Couture-Senécal; Gang Zheng; Warren C.W. Chan

doi:10.1038/s41563-020-0755-z

The dose threshold for nanoparticle tumour delivery

Ben Ouyang, Wilson Poon, Yi Nan Zhang, Zachary P. Lin, Benjamin R. Kingston, Anthony J. Tavares, Yuwei Zhang, Juan Chen, Michael S. Valic, Abdullah M. Syed, Presley MacMillan, Julien Couture-Senécal, Gang Zheng, Warren C.W. Chan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

392 Citations (Scopus)

Abstract

Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.

Original language	English
Pages (from-to)	1362-1371
Number of pages	10
Journal	Nature Materials
Volume	19
Issue number	12
DOIs	https://doi.org/10.1038/s41563-020-0755-z
Publication status	Published - Dec 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus Subject Areas

General Chemistry
General Materials Science
Condensed Matter Physics
Mechanics of Materials
Mechanical Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41563-020-0755-z

Cite this

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title = "The dose threshold for nanoparticle tumour delivery",

abstract = "Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.",

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AU - Ouyang, Ben

AU - Poon, Wilson

AU - Zhang, Yi Nan

AU - Lin, Zachary P.

AU - Kingston, Benjamin R.

AU - Tavares, Anthony J.

AU - Zhang, Yuwei

AU - Chen, Juan

AU - Valic, Michael S.

AU - Syed, Abdullah M.

AU - MacMillan, Presley

AU - Couture-Senécal, Julien

AU - Zheng, Gang

AU - Chan, Warren C.W.

PY - 2020/12

Y1 - 2020/12

N2 - Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.

AB - Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery: 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.

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The dose threshold for nanoparticle tumour delivery

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

Access to Document

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