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Increased nanoparticle penetration in collagenase-treated multicellular spheroids
Thomas T Goodman1, Peggy L Olive, Suzie H Pun
1Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
International Journal of Nanomedicine
|August 29, 2007
Summary
Nanoparticle delivery into solid tumors is limited by the extracellular matrix. Modifying nanoparticles with collagenase improves penetration of smaller particles, enhancing cancer treatment potential.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- The extracellular matrix (ECM) in solid tumors acts as a barrier, hindering nanoparticle penetration and limiting the effectiveness of nanomedicines for cancer therapy.
- Optimizing nanoparticle delivery vehicles is crucial for improving diagnostic and therapeutic outcomes in oncology.
Purpose of the Study:
- To investigate the impact of nanoparticle size and collagenase treatment on the penetration of nanoparticles within a tumor microenvironment model.
- To evaluate the efficacy of ECM-modulating enzymes, specifically collagenase, in enhancing nanoparticle delivery to solid tumors.
Main Methods:
- Utilized a multicellular spheroid model to simulate solid tumor conditions.
- Systematically assessed the penetration of carboxylated polystyrene nanoparticles of varying sizes (less than and greater than 100 nm).
- Investigated the effect of collagenase treatment on spheroid penetration and developed collagenase-coated nanoparticles for targeted ECM degradation.
Main Results:
- Nanoparticle penetration into the spheroid core was restricted to particles smaller than 100 nm.
- Collagenase treatment significantly enhanced the penetration of nanoparticles up to 100 nm.
- Collagenase-coated 100 nm nanoparticles showed a four-fold increase in core delivery compared to control nanoparticles.
Conclusions:
- Nanoparticle size is a critical factor for tumor penetration, with smaller particles (<100 nm) showing better access.
- Enzymatic degradation of the ECM using collagenase can significantly improve nanoparticle delivery into tumor cores.
- Incorporating ECM-modulating enzymes into nanoparticle formulations offers a promising strategy to enhance nanomedicine efficacy in solid tumors.

