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Cited by 733D Printing in Biomedical ResearchMicrofluidic and Capillary Electrophoresis ApplicationsNanoparticle-Based Drug Delivery

In vitro vascularized liver and tumor tissue microenvironments on a chip for dynamic determination of nanoparticle transport and toxicity

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Ozkan, Alican, Ghousifam, Neda, Hoopes, Paul Jack, Yankeelov, Thomas Edward, Rylander, Marissa Nichole·2019·Biotechnology and Bioengineering
DOI 10.1002/bit.26919PMC PMC10637916
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Abstract

This paper presents the development of a vascularized breast tumor and healthy or tumorigenic liver microenvironments‐on‐a‐chip connected in series. This is the first description of a vascularized multi tissue‐on‐a‐chip microenvironment for modeling cancerous breast and cancerous/healthy liver microenvironments, to allow for the study of dynamic and spatial transport of particles. This device enables the dynamic determination of vessel permeability, the measurement of drug and nanoparticle transport, and the assessment of the associated efficacy and toxicity to the liver. The platform is utilized to determine the effect of particle size on the spatiotemporal diffusion of particles through each microenvironment, both independently and in response to the circulation of particles in varying sequences of microenvironments. The results show that when breast cancer cells were cultured in the microenvironments they had a 2.62‐fold higher vessel porosity relative to vessels within healthy liver microenvironments. Hence, the permeability of the tumor microenvironment increased by 2.35‐ and 2.77‐fold compared with a healthy liver for small and large particles, respectively. The extracellular matrix accumulation rate of larger particles was 2.57‐fold lower than smaller particles in a healthy liver. However, the accumulation rate was 5.57‐fold greater in the breast tumor microenvironment. These results are in agreement with comparable in vivo studies. Ultimately, the platform could be utilized to determine the impact of the tissue or tumor microenvironment, or drug and nanoparticle properties, on transport, efficacy, selectivity, and toxicity in a dynamic, and high‐throughput manner for use in treatment optimization.

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  • Vessels in the breast tumor compartments were 2.62-fold more permeable to NPs than were vessels surrounded by healthy tissues.

    “For example, vessels in the breast tumor compartments were 2.62-fold more permeable to NPs than were vessels surrounded by healthy tissues.”

    From The Tumor-on-Chip: Recent Advances in the Development of Microfluidic Systems to Recapitulate the Physiology of Solid Tumors (2019) · cites this paper as [55]

    The Abstract reports that vessels in breast tumor microenvironments had 2.62-fold higher porosity than vessels in healthy liver microenvironments, not 2.62-fold higher nanoparticle permeability. It reports particle-size-dependent permeability increases of 2.35- and 2.77-fold instead. The claim captures the direction of the difference but assigns the porosity figure to permeability. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Ozkan, A., Ghousifam, N., Hoopes, P. J., Yankeelov, T. E., & Rylander, M. N.
Affiliations
  • Department of Mechanical Engineering The University of Texas at Austin Austin Texas
  • The University of Texas at Austin (US)
  • Dartmouth College (US)
ORCID
Venue
Biotechnology and Bioengineering
Publisher
Wiley
Published
2019-02-13
Volume
116
Issue
5
Pages
1201-1219
ISSN
  • 0006-3592 (ISSN-L)
  • 1097-0290
DOI
10.1002/bit.26919
PMC
PMC10637916
OpenAlex
W2892987557
Cited by
73
References
9
Citations by year
2026: 10 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 13 · 2021: 13 · 2020: 6 · 2019: 5 · 2018: 1
FWCI
3.26
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Biotechnology and Bioengineering (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • arXiv (Cornell University) (submittedVersion)
  • arXiv (Cornell University)
Funders
  • Foundation for the National Institutes of Health (R21EB019646)
  • Cancer Prevention and Research Institute of Texas (RR160005)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
  • Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
breast cancer, liver microenvironment, nanoparticle transport, nanoparticle toxicity, vascular permeability, particle size effects, extracellular matrix accumulation, tumor microenvironment, drug delivery
MeSH terms
Breast Neoplasms, Extracellular Matrix, Female, Humans, Liver Neoplasms, Neovascularization, Pathologic, Particle Size, Cell Line, Tumor, Nanoparticles, Lab-On-A-Chip Devices, Tumor Microenvironment

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