3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles
Abstract
The anticancer activity of compounds and nanoparticles is most often determined in the cell monolayer. However, three-dimensional (3D) systems, such as tumor spheroids, are more representing the natural tumor microenvironment. They have been shown to have higher invasiveness and resistance to cytotoxic agents and radiotherapy compared to cells growing in 2D monolayer. Furthermore, to improve the prediction of clinical efficacy of drugs, in the past decades, even more sophisticated systems, such as multicellular 3D cultures, closely representing natural tumor microenvironment have been developed. Those cultures are formed from either cell lines or patient-derived tumor cells. Such models are very attractive and could improve the selection of tested materials for clinical trials avoiding unnecessary expensive tests in vivo. The microenvironment in tumor spheroids is different, and those differences or the interaction between several cell populations may contribute to different tumor response to the treatment. Also, different types of nanoparticles may have different behavior in 3D models, depending on their nature, physicochemical properties, the presence of targeting ligands on the surface, etc. Therefore, it is very important to understand in which cases which type of tumor spheroid is more suitable for testing specific types of nanoparticles, which conditions should be used, and which analytical method should be applied.
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Multicellular tumor spheroids are appropriate systems for modeling tumor heterogeneity and microenvironmental complexity.
“Multicellular tumor spheroids are appropriate systems for modeling tumor heterogeneity and microenvironmental complexity [204,205,206].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [206]
Penetration is governed by the physicochemical characteristics of the drug or particle-including size, surface charge, shape, lipophilicity, and acid dissociation constant-as well as by the structural and biochemical properties of the spheroid, such as ECM density, extracellular pH gradients, and compactness of the cellular arrangement.
“Penetration is governed by the physicochemical characteristics of the drug or particle—including size, surface charge, shape, lipophilicity, and acid dissociation constant—as well as by the structural and biochemical properties of the spheroid, such as ECM density, extracellular pH gradients, and compactness of the cellular arrangement [99,206,290].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [206]
Prolonged treatments may result in partial disintegration of the spheroid structure, complicating morphological evaluation and making longitudinal comparisons unreliable.
“Prolonged treatments may result in partial disintegration of the spheroid structure, complicating morphological evaluation and making longitudinal comparisons unreliable [206].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [206]
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Tumor microenvironment and the role of mesenchymal stromal cells
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Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
“Multicellular tumor spheroids are appropriate systems for modeling tumor heterogeneity and microenvironmental complexity [204–206].”
- Authors
- Daunys, S., Janonienė, A., Januškevičienė, I., Paškevičiūtė, M., & Petrikaitė, V.
- Affiliations
- Vilnius University (LT)
- Lithuanian University of Health Sciences (LT)
- Venue
- Advances in experimental medicine and biology
- Publisher
- Springer International Publishing
- Published
- 2021
- Volume
- 1295
- Pages
- 243-270
- ISSN
- 0065-2598 (ISSN-L)
- 2214-8019
- OpenAlex
- W3127899697
- Cited by
- 32
- References
- 215
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 3
- FWCI
- 8.39
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Advances in experimental medicine and biology (publishedVersion)
- PubMed (publishedVersion)
- Lithuanian University of Health Sciences (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- tumor spheroids, 3D tumor models, nanoparticles, anticancer drug screening, tumor microenvironment, patient-derived tumor cells, nanoparticle physicochemical properties, drug resistance, in vitro tumor model
- MeSH terms
- Humans, Spheroids, Cellular, Cell Culture Techniques, Cell Line, Tumor, Nanoparticles, Tumor Microenvironment
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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