Synthetic tumor networks for screening drug delivery systems
Open accessAbstract
Tumor drug delivery is a complex phenomenon affected by several elements in addition to drug or delivery vehicle's physico-chemical properties. A key factor is tumor microvasculature with complex effects including convective transport, high interstitial pressure and enhanced vascular permeability due to the presence of "leaky vessels". Current in vitro models of the tumor microenvironment for evaluating drug delivery are oversimplified and, as a result, show poor correlation with in vivo performance. In this study, we report on the development of a novel microfluidic platform that models the tumor microenvironment more accurately, with physiologically and morphologically realistic microvasculature including endothelial cell lined leaky capillary vessels along with 3D solid tumors. Endothelial cells and 3D spheroids of cervical tumor cells were co-cultured in the networks. Drug vehicle screening was demonstrated using GFP gene delivery by different formulations of nanopolymers. The synthetic tumor network was successful in predicting in vivo delivery efficiencies of the drug vehicles. The developed assay will have critical applications both in basic research, where it can be used to develop next generation delivery vehicles, and in drug discovery where it can be used to study drug transport and delivery efficacy in realistic tumor microenvironment, thereby enabling drug compound and/or delivery vehicle screening.
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A vascularized microfluidic tumor model (MTM) consisting of a tumor compartment and a surrounding network of vessels, separated by a 2 μm wide porous interface, was developed and characterized.
“A vascularized MTM has been developed and characterized, consisting of a tumor compartment and a surrounding network of vessels, separated by a 2 μ m wide porous interface (Figure 1A,B). 17,21,26”
From Rapid Assessment of Nanoparticle Extravasation in a Microfluidic Tumor Model (2019) · cites this paper as [17]
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References 53 · Cited by 57
- Authors
- Prabhakarpandian, B., Shen, M.-C., Nichols, J. B., Garson, C. J., Mills, I. R., Matar, M. M., Fewell, J. G., & Pant, K.
- Affiliations
- CFD Research Corporation (United States) (US)
- Celsion (United States) (US)
- Corresponding author
- Prabhakarpandian, Balabhaskar
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 201
- Pages
- 49-55
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC4418523
- OpenAlex
- W2047762633
- Cited by
- 57
- References
- 53
- Citations by year
- 2024: 1 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 11 · 2018: 11 · 2017: 11 · 2016: 5 · 2015: 3
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1R43CA139841-01)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Keywords
- tumor drug delivery, tumor microenvironment, microfluidic tumor model, endothelial cells, tumor spheroids, cervical cancer cells, tumor microvasculature
- MeSH terms
- Cell Line, HeLa Cells, Humans, Neoplasms, Plasmids, Polymers, Drug Delivery Systems, Gene Transfer Techniques, Coculture Techniques, Endothelial Cells, Microfluidics, Green Fluorescent Proteins, Nanoparticles, Tumor Microenvironment
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