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Updated: Feb 3, 2026

A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Integration of hyper-compliant microparticles into a 3D melanoma tumor model
Manisha K Shah1, Elizabeth A Leary1, Eric M Darling2
1Center for Biomedical Engineering, Brown University, RI, USA.
Abstract:
Multicellular spheroids provide a physiologically relevant platform to study the microenvironment of tumors and therapeutic applications, such as microparticle-based drug delivery. The goal of this study was to investigate the incorporation/penetration of compliant polyacrylamide microparticles (MPs), into either cancer or normal human cell spheroids. Incorporation of collagen-1-coated MPs (stiffness: 0.1 and 9 kPa; diameter: 15-30 µm) into spheroids (diameter ∼100 µm) was tracked for up to 22 h. Results indicated that cells within melanoma spheroids were more influenced by MP mechanical properties than cells within normal cell spheroids. Melanoma spheroids had a greater propensity to incorporate and displace the more compliant MPs over time. Mature spheroids composed of either cell type were able to recognize and integrate MPs. While many tumor models exist to study drug delivery and efficacy, the study of uptake and incorporation of cell-sized MPs into established spheroids/tissues or tumors has been limited. The ability of hyper-compliant MPs to successfully penetrate 3D tumor models with natural extracellular matrix deposition provides a novel platform for potential delivery of drugs and other therapeutics into the core of tumors and micrometastases.
Insights
Researchers studied how compliant microparticles (MPs) enter cancer and normal cell spheroids. Melanoma cells incorporated softer MPs more readily, suggesting potential for targeted drug delivery to tumors.
Area of Science:
- Biomedical Engineering
- Materials Science
- Cancer Research
Background:
- Multicellular spheroids mimic tumor microenvironments, crucial for studying drug delivery.
- Understanding microparticle (MP) interaction with spheroids is key for therapeutic applications.
- Limited studies exist on cell-sized MP uptake into 3D tumor models.
Purpose of the Study:
- To investigate the incorporation and penetration of compliant polyacrylamide microparticles (MPs) into cancer and normal human cell spheroids.
- To assess the influence of MP mechanical properties on spheroid interaction.
Main Methods:
- Collagen-1-coated polyacrylamide MPs (stiffness: 0.1 and 9 kPa; diameter: 15-30 µm) were introduced into spheroids (diameter ~100 µm).
- MP incorporation and penetration were tracked for up to 22 hours.
- Comparison between melanoma and normal human cell spheroids was performed.
Main Results:
- Mature spheroids of both cell types recognized and integrated MPs.
- Melanoma spheroids showed greater influence from MP mechanical properties compared to normal cell spheroids.
- Melanoma spheroids exhibited a higher tendency to incorporate and displace more compliant MPs over time.
Conclusions:
- Hyper-compliant MPs can penetrate 3D tumor models with natural extracellular matrix.
- This suggests a novel platform for delivering therapeutics to the core of tumors and micrometastases.
- MP compliance significantly impacts interaction with melanoma spheroids, offering potential for targeted therapies.
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