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Introduction: The lack of an appropriate in vitro model of the tumor microenvironment is one of the largest obstacles in evaluating preclinical cancer drug screenings.1 Cancer cell monolayers do not effectively mimic the limited drug penetration properties of the complex tumor structures found in cancer patients. 3-D multicellular tumor spheroids (MCTS) serve as a more effective model as they better resemble cancer in structure as well as limited drug penetration. In our experiments, we created heterospheroids composed of 4T1 breast tumor cells and 3T3 fibroblasts, as well as homospheroids of each cell type. Tumors feature stromal and extracellular matrix components in addition to cancer cells in ratios that vary between different types of cancer. Fibroblasts are the major component of cancer stroma as well as producers of extracellular matrix. Since heterospheroids feature 3T3 fibroblasts, they may better model the diverse tumor microenvironment.2 We also synthesized fluorescent PLGA nanoparticles that were added to our spheroid cultures. Using confocal microscopy and ImageJ’s fluorescence measuring tools, we qualitatively and quantitatively evaluated the drug penetration properties of our spheroids.
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Analytical Solution of the Effects of Applied Electrical Field to Drug Delivery in Electrochemotherapy
This study investigates electrochemotherapy by introducing a modified mathematical formulation that captures the effects of an applied DC electrical field on the penetration of chemotherapeutic drugs into tumorous cells. The model uses differential equations (second order) based on a cylindrical depiction of a blood vessel as the drug source. Drug concentration is treated as radially distributed at steady state, with the influence of the electrical field incorporated through an additional evaluation, and electroporation-driven tumor uptake modeled as a first-order chemical reaction. Nondimensionalization is applied to broaden applicability across scenarios, and a unique solution is proposed using the modified Bessel function. The resulting equations yield simulated predictions for drug penetration depth under varying applied electrical fields and the fraction of tumorous cells killed, with noted needs for improved linkage to tumor microenvironments and realistic electrical-field distributions.
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- Award ID(s):
- 2345379
- PAR ID:
- 10662907
- Publisher / Repository:
- American Institute of Chemical Engineers (AIChE)
- Date Published:
- Edition / Version:
- 1
- Page Range / eLocation ID:
- 1-2
- Subject(s) / Keyword(s):
- electrochemotherapy electrophoresis bessel functions
- Format(s):
- Medium: X Size: 128KB Other: pdf
- Size(s):
- 128KB
- Location:
- Boston, MA, USA
- Sponsoring Org:
- National Science Foundation
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