Abstract

To have the desired therapeutic effect, nanomedicines and macromolecular medications must move from the site of injection to the site of action, without having adverse effects. Transvascular transport is a critical step of this navigation, as exemplified by the Enhanced Permeability and Retention (EPR) effect in solid tumors, not found in normal organs. Numerous studies have concluded that passive, diffusion- and convection-based transport predominates over active, cellular mechanisms in this effect. However, recent work using a new approach reevaluated this principle by comparing tumors with or without fixation and concluded the opposite. Here, we address the controversy generated by this new approach by reporting evidence from experimental investigations and computer simulations that separate the contributions of active and passive transport. Our findings indicate that tissue fixation reduces passive transport as well as active transport, indicating the need for new methods to distinguish the relative contributions of passive and active transport.

Details

Title
Fixation alters the physical properties of tumor tissue that regulate nanomedicine transport
Author
Martin, John D 1 ; Mpekris, Fotios 2 ; Chauhan, Vikash P 3 ; Martin, Margaret R 4 ; Walsh, Megan E 5 ; Stuber, Matthew D 6 ; McDonald, Donald M 7 ; Fan, Yuan 8 ; Stylianopoulos, Triantafyllos 2 ; Jain, Rakesh K 9 

 Materia Therapeutics, Las Vegas, NV, USA 
 Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus 
 Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA 
 Department of Computer Science, Tufts University, Medford, MA, USA 
 Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, USA 
 Process Systems and Operations Research Laboratory, Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, USA 
 Helen Diller Family Comprehensive Cancer Center, Department of Anatomy, University of California, San Francisco, CA, USA 
 Department of Biomedical Engineering, Duke University, Durham, NC, USA 
 Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA 
Publication year
2024
Publication date
Dec 2024
Publisher
Taylor & Francis Ltd.
ISSN
10717544
e-ISSN
15210464
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3134584177
Copyright
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons  Attribution – Non-Commercial License http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.