Description
Current research suggests that the altered tumor microenvironment may drive cancer aggression and metastatic potential. Nanoparticles have unique imaging and therapeutic possibilities arising from their small size, surface tailorability, and binding capability. If properly designed nanoparticle may exploit the disordered architecture, increased vessel density, large pores, hyperpermeability, and other abnormalities characteristic of the vasculature in tumors and achieve increased accumulation in cancerous tissue. In order to optimize the diagnostic and therapeutic methods, it is necessary to understand the transport processes occurring in the breast and the changes that take place with the disease. The mixture theory model of the fluid and solute transport in the microvasculature of normal and malignant tissues is a powerful tool that overcomes the handicap of existing transport models based on classical equations. This model accounts for transport in the vessel lumen, vessel wall, and the interstitial space separately. The numerical analysis incorporated through this model delineates the dependence of hydraulic permeability coefficient and hydraulic conductivity on solute concentration. The novelty of the approach is that it allows inclusion of external body forces, solid deformation, solute–solid and solute–solute interactions. In this study, we use the mixture theory model to develop a fully three-dimensional geometrical model of the tumor microenvironment platform incorporating a physiological concentration of nanoparticle solutes through blood flow embedded in an extracellular collagen matrix. We quantify cell response to solute gradients of varying magnitude formed by diffusion of nanoparticles from one channel into the surrounding ECM. The governing equations are solved herein for an axisymmetric cell model using Comsol 3.2 .The cell is comprised of two constant diameter channels embedded in a cylinder of tissue. It is subdivided along its length into terminal segments of arteriole, effective parallel capillaries, and postcapillary venules The 800-µm apart parallel channels allow development of stable concentration gradients in the system. The radius of the unit cell and the capillary length reflect the increased vessel density typical of tumors. The arteriole pressure of 4396 Pa is specified at the inlet and a venule pressure of 2000 Pa is specified at the outlet of both microchannels. At the perimeter of the unit, vessel pressure is assumed to be constant. At the interface of the intravascular and extravascular space, the modified version of Starling’s law is used as the capillary wall boundary condition. The gradient is induced by specifying a solute concentration at the inlet of one of the microchannels. Two cases of extracellular matrix stiffness were investigated. The first ECM condition designated as “soft” is designed for a compression modulus of 2000 Pa, whereas the second condition designated as “stiff” corresponds to a compression modulus of 4000 Pa, each condition representing premalignant breast stiffness and malignant breast tissue respectively. This study characterizes the three dimensional microenvironment which has a stupendous effect on cell morphology, signaling and migration through mechanical and structural interactions, but its fidelity could not be successfully accounted for in earlier experimental studies.
Recommended Citation
Chakaborty, S., Schuff, M., Nauman, E., Vlachos, P., Antoine, E., & Rylander, M. (2014). Mixture theory study of nanoparticle transport in breast cancer tissues. In A. Bajaj, P. Zavattieri, M. Koslowski, & T. Siegmund (Eds.). Proceedings of the Society of Engineering Science 51st Annual Technical Meeting, October 1-3, 2014 , West Lafayette: Purdue University Libraries Scholarly Publishing Services, 2014. https://docs.lib.purdue.edu/ses2014/bio/nba/10
Mixture theory study of nanoparticle transport in breast cancer tissues
Current research suggests that the altered tumor microenvironment may drive cancer aggression and metastatic potential. Nanoparticles have unique imaging and therapeutic possibilities arising from their small size, surface tailorability, and binding capability. If properly designed nanoparticle may exploit the disordered architecture, increased vessel density, large pores, hyperpermeability, and other abnormalities characteristic of the vasculature in tumors and achieve increased accumulation in cancerous tissue. In order to optimize the diagnostic and therapeutic methods, it is necessary to understand the transport processes occurring in the breast and the changes that take place with the disease. The mixture theory model of the fluid and solute transport in the microvasculature of normal and malignant tissues is a powerful tool that overcomes the handicap of existing transport models based on classical equations. This model accounts for transport in the vessel lumen, vessel wall, and the interstitial space separately. The numerical analysis incorporated through this model delineates the dependence of hydraulic permeability coefficient and hydraulic conductivity on solute concentration. The novelty of the approach is that it allows inclusion of external body forces, solid deformation, solute–solid and solute–solute interactions. In this study, we use the mixture theory model to develop a fully three-dimensional geometrical model of the tumor microenvironment platform incorporating a physiological concentration of nanoparticle solutes through blood flow embedded in an extracellular collagen matrix. We quantify cell response to solute gradients of varying magnitude formed by diffusion of nanoparticles from one channel into the surrounding ECM. The governing equations are solved herein for an axisymmetric cell model using Comsol 3.2 .The cell is comprised of two constant diameter channels embedded in a cylinder of tissue. It is subdivided along its length into terminal segments of arteriole, effective parallel capillaries, and postcapillary venules The 800-µm apart parallel channels allow development of stable concentration gradients in the system. The radius of the unit cell and the capillary length reflect the increased vessel density typical of tumors. The arteriole pressure of 4396 Pa is specified at the inlet and a venule pressure of 2000 Pa is specified at the outlet of both microchannels. At the perimeter of the unit, vessel pressure is assumed to be constant. At the interface of the intravascular and extravascular space, the modified version of Starling’s law is used as the capillary wall boundary condition. The gradient is induced by specifying a solute concentration at the inlet of one of the microchannels. Two cases of extracellular matrix stiffness were investigated. The first ECM condition designated as “soft” is designed for a compression modulus of 2000 Pa, whereas the second condition designated as “stiff” corresponds to a compression modulus of 4000 Pa, each condition representing premalignant breast stiffness and malignant breast tissue respectively. This study characterizes the three dimensional microenvironment which has a stupendous effect on cell morphology, signaling and migration through mechanical and structural interactions, but its fidelity could not be successfully accounted for in earlier experimental studies.