Related Experiment Video
Updated: Mar 15, 2026
10:44
Author Spotlight: In Vitro Hydrogel Model for Glioblastoma Microenvironment Study
Published on: September 22, 2023
2.3K
Tumor stroma-containing 3D spheroid arrays: A tool to study nanoparticle penetration
Dwi L Priwitaningrum1, Jean-Baptiste G Blondé2, Adithya Sridhar2
1Targeted Therapeutics, Department of Biomaterials Science and Technology, MIRA Institute, University of Twente, Enschede, The Netherlands.
Summary
Tumor stroma significantly hinders nanoparticle penetration, impacting drug delivery. A novel 3D co-culture model effectively mimics this barrier, aiding the design of nanoparticles with improved tumor penetration for better therapeutic effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Nanoparticle distribution within tumors is crucial for therapeutic efficacy.
- Tumor stroma, rich in cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM), impedes nanoparticle penetration.
- A lack of suitable in vitro models hinders the study of nanoparticle penetration through tumor stroma.
Purpose of the Study:
- To develop and characterize a 3D co-culture spheroidal array mimicking tumor stroma.
- To investigate the penetration of silica and PLGA nanoparticles within this model.
- To evaluate the influence of stroma composition on nanoparticle penetration.
Main Methods:
- Characterization of human breast tumor biopsies for stroma content (α-SMA, collagen-1).
- Development of 3D homospheroids and heterospheroids using cancer cells and fibroblasts in a microwell array.
- Investigation of nanoparticle (silica, PLGA) penetration using confocal microscopy and fluorescent imaging.
Main Results:
- Heterospheroids showed increased α-SMA and collagen, mimicking clinical tumor stroma.
- Increasing fibroblast content in spheroids significantly inhibited nanoparticle penetration.
- Smaller (30nm) and highly negatively charged nanoparticles demonstrated deeper penetration.
Conclusions:
- Tumor stroma presents a significant barrier to nanoparticle penetration.
- The developed 3D co-culture platform accurately models tumor stroma for nanoparticle penetration studies.
- Optimizing nanoparticle size and surface charge is key for enhanced tumor drug delivery.
