Spatio‐temporal modeling of nanoparticle delivery to multicellular tumor spheroids
- 24 March 2008
- journal article
- research article
- Published by Wiley in Biotechnology & Bioengineering
- Vol. 101 (2), 388-399
- https://doi.org/10.1002/bit.21910
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, 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. Biotechnol. Bioeng. 2008;101: 388–399.This publication has 27 references indexed in Scilit:
- Exploiting the enhanced permeability and retention effect for tumor targetingDrug Discovery Today, 2006
- Tumor Vascular Permeability, Accumulation, and Penetration of Macromolecular Drug CarriersJNCI Journal of the National Cancer Institute, 2006
- Proteolytic Surface Functionalization Enhancesin VitroMagnetic Nanoparticle Mobility through Extracellular MatrixNano Letters, 2006
- The Penetration of Anticancer Drugs through Tumor Tissue as a Function of Cellular Adhesion and Packing Density of Tumor CellsCancer Research, 2006
- Resistance of Tumor Interstitial Pressure to the Penetration of Intraperitoneally Delivered Antibodies into Metastatic Ovarian TumorsClinical Cancer Research, 2005
- Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosisBiochemical Journal, 2004
- Interaction of Anionic Superparamagnetic Nanoparticles with Cells: Kinetic Analyses of Membrane Adsorption and Subsequent InternalizationLangmuir, 2002
- Delivery of molecular and cellular medicine to solid tumorsAdvanced Drug Delivery Reviews, 2001
- Effect of therapeutic macromolecules in spheroidsCritical Reviews in Oncology/Hematology, 2000
- Effects of hyaluronidase on doxorubicin penetration into squamous carcinoma multicellular tumor spheroids and its cell lethalityZeitschrift für Krebsforschung und Klinische Onkologie, 1994