Fixation alters the physical properties of tumor tissue that regulate nanomedicine transport
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.
Authors
- Donald M. McDonald (ORCID: https://orcid.org/0000-0002-6985-9564)
- M. Walsh (ORCID: https://orcid.org/0009-0009-2293-6049)
- Fan Yuan (ORCID: https://orcid.org/0000-0002-0687-6607)
- John D. Martin (ORCID: https://orcid.org/0000-0002-9828-8203)
- Fotios Mpekris (ORCID: https://orcid.org/0000-0002-7125-4062)
- Matthew D. Stuber (ORCID: https://orcid.org/0000-0001-8435-9552)
- Vikash P. Chauhan (ORCID: https://orcid.org/0000-0001-9126-2302)
- Triantafyllos Stylianopoulos (ORCID: https://orcid.org/0000-0002-3093-1696)
- Margaret R. Martin
- Rakesh K. Jain
Institutions
- Tufts University (US)
- Harvard University (US)
- University of Connecticut (US)
- Duke University (US)
- University of California, San Francisco (US)
- University of Cyprus (CY)
- Massachusetts General Hospital (US)
- Materia (United States) (US)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
- Massachusetts Institute of Technology (US)
- Carnegie Mellon University (US)
Publication Details
- Journal
- Drug Delivery
- Published
- 2024-11-20
- DOI
- https://doi.org/10.1080/10717544.2024.2430528
- Primary Topic
- Nanoparticle-Based Drug Delivery
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Foundation for Cancer Research
- Advanced Medical Research Foundation
- Ludwig Center at Harvard
- National Heart, Lung, and Blood Institute
- HORIZON EUROPE European Research Council