ArticleIntegrative biology : quantitative biosciences from nano to macro2013
Microfluidic technique to measure intratumoral transport and calculate drug efficacy shows that binding is essential for doxorubicin and release hampers Doxil.
Article in Integrative biology : quantitative biosciences from nano to macro, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed.
- Development of Magnetic Microbeads Equipped with Temperature-Responsive Artificial Antibodies for Efficient Anticancer Drug Administration.Analytical chemistry · 2026Article
- In vitro cellular interaction of drug-loaded liposomes with 2D and 3D cell culture of U87-MG cell line.PloS one · 2025Article
- A comprehensive overview of advanced dynamicTissue barriers · 2024Review
- Chicken embryo model forInternational journal of pharmaceutics: X · 2023Article
- Fabrication of Doxorubicin-Loaded Lipid-Based Nanocarriers by Microfluidic Rapid Mixing.Biomedicines · 2022Article
- Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach.Scientific reports · 2021Article
- Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response.Communications biology · 2021Article
- From 2D to 3D Cancer Cell Models-The Enigmas of Drug Delivery Research.Nanomaterials (Basel, Switzerland) · 2020Review
- Intra-tumoral drug concentration mapping within solid tumor micro-milieu using in-vitro model and doxorubicin as a model drug.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- The motility regulator flhDC drives intracellular accumulation and tumor colonization of Salmonella.Journal for immunotherapy of cancer · 2019Article
- Predicting drug delivery efficiency into tumor tissues through molecular simulation of transport in complex vascular networks.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
- Tissue transport affects how treatment scheduling increases the efficacy of chemotherapeutic drugs.Journal of theoretical biology · 2018Article
- Differential response to doxorubicin in breast cancer subtypes simulated by a microfluidic tumor model.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2017Review
- Engineered bacteria detect spatial profiles in glucose concentration within solid tumor cell masses.Biotechnology and bioengineering · 2016Article
- Trg-deficient Salmonella colonize quiescent tumor regions by exclusively penetrating or proliferating.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Effect of small-molecule modification on single-cell pharmacokinetics of PARP inhibitors.Molecular cancer therapeutics · 2014Article
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Authors and funding
4 authors.
Funding
Abstract
Intratumoral transport and binding are important mechanisms that determine the efficacy of cancer drugs. Current drug screening methods rely heavily on monolayers of cancer cells, which overlook the contribution of tissue-level transport and binding. To quantify these factors, we developed a method that couples an in vitro, drug-delivery device containing a three-dimensional cell mass and a mathematical model of drug diffusion, binding to DNA, release from carriers, and clearance. Spheroids derived from LS174T human colon carcinoma cells were inserted into rectangular chambers to form rectangular cell masses (tissue) and subjected to continuous medium perfusion. To simulate drug delivery and clearance, the tissues were treated with doxorubicin followed by drug-free medium. To evaluate the effect of liposome encapsulation, tissues were treated with liposome-encapsulated doxorubicin (Doxil). Spatiotemporal dynamics of drug distribution and apoptosis was measured by fluorescence microscopy. The diffusivity and DNA binding constant of doxorubicin were determined by fitting experimental data to the mathematical model. Results show that an ideal combination of diffusivity, binding constant, clearance rate, and cytotoxicity contribute to the high therapeutic efficacy of doxorubicin. There was no detectable release of doxorubicin from Doxil in the tissues. The rate of doxorubicin release, evaluated by fitting experimental data to the mathematical model, was below therapeutically effective levels. These results show that despite enhanced systemic circulation obtained by liposome encapsulation, the therapeutic effect of Doxil is limited by slow intratumoral drug release. The experimental and computational methods developed here to calculate drug efficacy provide mechanisms to explain poor performance of drug candidates, and enable design of more successful cancer drugs.
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