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Vaupel, P.* ; Multhoff, G.

Pathophysiological barriers impeding the delivery of Heat Shock Protein (HSP)-based macromolecules and nanotherapeutics to solid tumors.

In: Cellular Trafficking of Cell Stress Proteins in Health and Disease. Heidelberg: Springer, 2012. 185-199 (Heat Shock Proteins; 6)

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The chaotic microvasculature of solid tumors leads to significant impediment of delivery, uneven distribution and compromised penetration of macromolecules and nanotherapeutics from tumor microvessels across the interstitial compartment to cancer cells, especially to cells distant from microvessels. To reach viable tumor cells in a relevant concentration, diagnostic and therapeutic agents are confronted with several obstacles: disturbed convective transport within the chaotic vascular compartment, spatio-temporally uneven distribution within the tissue, and significant shunt flow bypassing the exchange processes between the vascular bed and the extravascular space. Extravasation and extravascular convection of macromolecules and nanoparticles are mainly impaired by high interstitial fluid pressure. Furthermore, marked gradients in concentrations of macromolecules and nanoparticles exist within the extravascular space limiting anticancer activities with increasing distance from tumor blood vessels.

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Publication type Article: Edited volume or book chapter

Editors Henderson, B.* ; Pockley, A.G.*

Corresponding Author

Keywords Heat shock protein-based therapies; Tumor blood flow; Tumor vasculature; Diffusional transport; Convective transport; Transport barriers; Extravasation; Interstitial transport; Tumor interstitium; Interstitial hypertension; Intratumor pharmacokinetics

ISBN 978-94-007-4739-5

Book Volume Title Cellular Trafficking of Cell Stress Proteins in Health and Disease

Quellenangaben Pages: 185-199

Series Heat Shock Proteins; 6

Publisher Springer

Publishing Place Heidelberg

Non-patent literature Publications

Institute(s) Institute of Biological and Medical Imaging (IBMI)