Integration of hyper-compliant microparticles into a 3D melanoma tumor model |
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| Institution: | 1. Center for Biomedical Engineering, Brown University, RI, USA;2. Department of Molecular Pharmacology, Physiology, and Biotechnology, Brown University, RI, USA;3. Department of Orthopaedics, Brown University, RI, USA;4. School of Engineering, Brown University, RI, USA;1. Department of Otolaryngology-Head and Neck Surgery, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;2. Graduate Program in Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;3. Department of Statistical Science, Southern Methodist University, Dallas, TX 75275, USA;4. Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;1. Institut des Biomolécules Max Mousseron (UMR 5247 CNRS—Université de Montpellier 1—Université de Montpellier 2), place Eugène Bataillon CC 1706, 34095 Montpellier Cedex 5, France;2. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo n. 2, 166 10 Prague 6, Czech Republic;1. Department of Physical Education, Federal University of São Carlos, São Carlos, Brazil;2. Laboratory of Functional Morphology, Department of Biology, University of Antwerp, Antwerp, Belgium;3. Department of Rehabilitation Sciences and Physiotherapy, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium;5. Bioengineering and Biomechanics Laboratory, Federal University of Goiás, Goiânia, Brazil |
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| 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. |
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| Keywords: | Particle penetration Spheroid High-throughput Drug delivery |
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