Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip
Open accessAbstract
Delivery of therapeutic agents selectively to tumor tissue, which is referred as "targeted delivery," is one of the most ardently pursued goals of cancer therapy. Recent advances in nanotechnology enable numerous types of nanoparticles (NPs) whose properties can be designed for targeted delivery to tumors. In spite of promising early results, the delivery and therapeutic efficacy of the majority of NPs are still quite limited. This is mainly attributed to the limitation of currently available tumor models to test these NPs and systematically study the effects of complex transport and pathophysiological barriers around the tumors. In this study, thus, we developed a new in vitro tumor model to recapitulate the tumor microenvironment determining the transport around tumors. This model, named tumor-microenvironment-on-chip (T-MOC), consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid. Using this T-MOC platform, the transport of NPs and its variation due to tumor microenvironmental parameters have been studied including cut-off pore size, interstitial fluid pressure, and tumor tissue microstructure. The results suggest that T-MOC is capable of simulating the complex transport around the tumor, and providing detailed information about NP transport behavior. This finding confirms that NPs should be designed considering their dynamic interactions with tumor microenvironment.
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These results suggest that the in vivo size window for effective NP tumor uptake could be narrower than that referred in literature and mainly based on the EPR paradigm; indeed, NPs smaller than 100 nm in diameter could be more effective.
“Also, these results suggest that the in vivo size window for effective NP tumor uptake could be narrower than that referred in literature and mainly based on the enhanced permeability and retention (EPR) paradigm; indeed, NPs smaller than 100 nm in diameter could be more effective.”
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 [28]
The Results and Discussion (page unavailable) say the effective size window may be narrower than EPR-based estimates: 100 nm particles transported rapidly in the chip model, whereas transport fell notably at 200 nm. The paper does not establish that particles smaller than 100 nm are more effective; 100 nm was the smallest size tested in the reported size comparison. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe tumor-on-chip device developed by Kwak et al. emulated the complex dynamics around the tumor, yielding detailed information about nanoparticle transport within a tumor niche.
“The results suggested that this tumor-on-chip device emulated the complex dynamics around the tumor, yielding detailed information about NP transport within a tumor niche.”
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 [28]
Kwak et al. results suggested that particle size was a key determinant of intra-tumor transport.
“Their results suggested that transmembrane transport was much faster than the interstitial diffusion inside the tumor and that particle size was a key determinant of intra-tumor transport.”
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 [28]
Kwak et al. results suggested that transmembrane transport was much faster than the interstitial diffusion inside the tumor.
“Their results suggested that transmembrane transport was much faster than the interstitial diffusion inside the tumor and that particle size was a key determinant of intra-tumor transport.”
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 [28]
Valuable information has been obtained from tumor-on-chip models for studying NP transport and penetration into the tumor niche.
“By contrast, valuable information has been obtained from tumor-on-chip models [21,27,28,47,64] as indicated by the following notable examples of tumor-on-chip platforms used to study NP transport and penetration into the tumor niche.”
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 [28]
This study shows that, to ensure the effective delivery of anticancer agents to tumors, NPs need to be sufficiently smaller than the endothelium cut-off pore size.
“This study shows that, to ensure the effective delivery of anticancer agents to tumors, NPs need to be sufficiently smaller than the endothelium cut-off pore size [28].”
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 [28]
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- Authors
- Kwak, B., Ozcelikkale, A., Shin, C. S., Park, K., & Han, B.
- Affiliations
- Purdue University West Lafayette (US)
- Corresponding author
- Han, Bumsoo
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 194
- Pages
- 157-167
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC4252353
- OpenAlex
- W1994967705
- Cited by
- 165
- References
- 45
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 13 · 2023: 12 · 2022: 19 · 2021: 19 · 2020: 17 · 2019: 18 · 2018: 16 · 2017: 16 · 2016: 13 · 2015: 3
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- OpenMETU (Middle East Technical University) (submittedVersion, cc-by-nc-nd)
- Funders
- NSF (CBET-1009465)
- NIH (CA129287, UL1 TR000006)
- Indiana Clinical and Translational Sciences Institute
- B.S.F. Schaefer Award
- Discovery Park Fellowship
- Purdue University
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- nanoparticle transport, tumor microenvironment, targeted drug delivery, in vitro tumor model, microfluidics, interstitial fluid pressure, pore size, tissue microstructure, extracellular matrix, endothelial cells, cancer nanomedicine
- MeSH terms
- Capillaries, Cells, Cultured, Computer Simulation, Extracellular Matrix, Female, Humans, Neoplasms, Particle Size, Drug Delivery Systems, Endothelial Cells, Microfluidics, Extracellular Fluid, Cell Line, Tumor, Nanoparticles, Tumor Microenvironment, MCF-7 Cells
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