Spatio-temporal modeling of nanoparticle delivery to multicellular tumor spheroids Export

@article{citeulike:2583370, abstract = {The inefficiency of nanoparticle penetration in tissues limits the therapeutic efficacy of such formulations for cancer applications. Recent work has indicated that modulation of tissue architecture with enzymes such as collagenase significantly increases macromolecule delivery. In this study we developed a mathematical model of nanoparticle penetration into multicellular spheroids that accounts for radially-dependent changes in tumor architecture, as represented by the volume fraction of tissue accessible to nanoparticle diffusion. Parameters such as nanoparticle binding and internalization rate constants and accessible volume fraction were determined experimentally. Unknown parameters of nanoparticle binding sites per cell in the spheroid and pore shape factor were determined by fitting to experimental data. The model was correlated with experimental studies of the penetration of 40 nm nanoparticles in SiHa multicellular spheroids with and without collagenase treatment and was able to accurately predict concentration profiles of nanoparticles within spheroids. The model was also used to investigate the effects of nanoparticle size. This model contributes toward the understanding of the role of tumor architecture on nanoparticle delivery efficiency. {\copyright} 2008 Wiley Periodicals, Inc.}, address = {Department of Bioengineering, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA; School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA}, author = {Goodman, Thomas T. and Chen, Jingyang and Matveev, Konstantin and Pun, Suzie H.}, citeulike-article-id = {2583370}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/bit.21910}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18500767}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18500767}, citeulike-linkout-3 = {http://www3.interscience.wiley.com/cgi-bin/abstract/117946384/ABSTRACT}, doi = {10.1002/bit.21910}, journal = {Biotechnology and Bioengineering}, keywords = {jing, modeling}, number = {999A}, pages = {n/a+}, posted-at = {2008-03-25 05:07:27}, priority = {2}, title = {Spatio-temporal modeling of nanoparticle delivery to multicellular tumor spheroids}, url = {http://dx.doi.org/10.1002/bit.21910}, volume = {9999}, year = {2008} }

TY - JOUR ID - citeulike:2583370 L3 - citeulike-article-id:2583370 N2 - The inefficiency of nanoparticle penetration in tissues limits the therapeutic efficacy of such formulations for cancer applications. Recent work has indicated that modulation of tissue architecture with enzymes such as collagenase significantly increases macromolecule delivery. In this study we developed a mathematical model of nanoparticle penetration into multicellular spheroids that accounts for radially-dependent changes in tumor architecture, as represented by the volume fraction of tissue accessible to nanoparticle diffusion. Parameters such as nanoparticle binding and internalization rate constants and accessible volume fraction were determined experimentally. Unknown parameters of nanoparticle binding sites per cell in the spheroid and pore shape factor were determined by fitting to experimental data. The model was correlated with experimental studies of the penetration of 40 nm nanoparticles in SiHa multicellular spheroids with and without collagenase treatment and was able to accurately predict concentration profiles of nanoparticles within spheroids. The model was also used to investigate the effects of nanoparticle size. This model contributes toward the understanding of the role of tumor architecture on nanoparticle delivery efficiency. © 2008 Wiley Periodicals, Inc. IS - 999A JF - Biotechnology and Bioengineering AD - Department of Bioengineering, University of Washington, 1705 NE Pacific Street, Seattle, WA 98195, USA; School of Mechanical and Materials Engineering, Washington State University, Pullman, WA 99164, USA TI - Spatio-temporal modeling of nanoparticle delivery to multicellular tumor spheroids VL - 9999 SP - n/a KW - jing KW - modeling AU - Goodman, Thomas AU - Chen, Jingyang AU - Matveev, Konstantin AU - Pun, Suzie PY - 2008/// UR - http://dx.doi.org/10.1002/bit.21910 ER -