Complete Disaggregation of MCF-7-derived Breast Tumour Spheroids with Very Low Concentrations of α-Mangostin Loaded in CD44 Thioaptamer-tagged Nanoparticles
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Background: α-Mangostin (αMG) is a natural substance that exerts a wide range of antitumor effects.Recently, we described that free αMG was able to dissociate multicellular tumour spheroids (MCTSs) generated from breast carcinoma cells and to reduce their cellular viability and motility.Here, αMG was encapsulated into lipidic nanoparticles (NPs), conjugated or not to a CD44 thioaptamer, and the anticancer action evaluated against MCF-7 breast MCTSs.Methods: NPs containing αMG were formulated with a core of polylactic-co-glycolyc acid.Some of them were decorated with a CD44 thioaptamer using as catalysts 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide.Both size and density of MCF-7-derived MCTSs were monitored during 72 h of treatment with NPs carrying 0.1, 0.5 and 1.0 µg/ml final concentrations of αMG.MCTSs were cultured on Matrigel or gelatine to better simulate the extracellular environment.Results: The NPs without thioaptamer and conveying 0.1 µg/ml αMG caused a significant dissociation of the MCTSs grown in gelatine after 24 h of treatment (p < 0.01).The most significant disaggregation of MCTSs was obtained using NPs carrying 0.5 µg/ml αMG (p < 0.01).A similar dissociating effect was observed when MCTSs were cultured in Matrigel under the same conditions for 48 -72 h.By contrast, only concentrations over 1.0 µg/ml of free αMG were able to provoke a damage to MCTSs, consisting in a substantial reduction in their size (p < 0.05).Since the MCTS dissociation induced by αMG-loaded NPs occurred only in the presence of Matrigel or gelatine, an impairment of cell contacts to collagen fibres was likely responsible of this effect.Finally, the treatment of MCTSs with αMG-loaded NPs that were conjugated to the CD44 thioaptamer caused a similar decrease in density but a lower expansion of the spheroid, suggesting that a significant number of cells were died or arrested in cycle.Conclusion: Very low concentrations of αMG delivered by lipidic NPs are sufficient to provoke a substantial disaggregation of MCF-7 MCTSs that involves cell-to-collagen contacts.Similarly, the treatment of MCTSs with NPs conjugated to a CD44 thioaptamer leads to MCTS dissociation but through a more damaging action that causes also a reduction in cell number.
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In spheroid-based assays, drug efficacy is often assessed by comparing changes in spheroid size over time relative to untreated controls.
“In spheroid-based assays, drug efficacy is often assessed by comparing changes in spheroid size over time relative to untreated controls [301,302,303].”
From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [301]
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Shah, S., & D’Souza, G. G. M. (2025) · Cells · doi:10.3390/cells14100732 · Cited by 66 · see citing works
“In spheroid-based assays, drug efficacy is often assessed by comparing changes in spheroid size over time relative to untreated controls [301–303].”
3D Tumor Spheroid Models for In Vitro Therapeutic Screening of Nanoparticles
Daunys, S., Janonienė, A., Januškevičienė, I., Paškevičiūtė, M., & Petrikaitė, V. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-58174-9_11 · Cited by 32 · see citing works
- Authors
- Bonafè, F., Pazzini, C., Marchionni, S., Guarnieri, C., & Muscari, C.
- Affiliations
- University of Bologna (IT)
- Corresponding author
- Muscari, Claudio
- Venue
- International Journal of Medical Sciences
- Publisher
- Ivyspring International Publisher
- Published
- 2019
- Volume
- 16
- Issue
- 1
- Pages
- 33-42
- ISSN
- 1449-1907 (ISSN-L)
- PMC
- PMC6332479
- OpenAlex
- W2904277448
- Cited by
- 18
- References
- 1
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 2
- FWCI
- 0.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- International Journal of Medical Sciences (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc)
- Funders
- Fondazione del Monte di Bologna e Ravenna
- Università di Bologna
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Natural Compound Pharmacology Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- α-mangostin, tumor spheroids, lipid nanoparticles, PLGA nanoparticles, MCF-7 cells, targeted drug delivery, anticancer activity, nanoparticle conjugation, extracellular matrix mimics, Matrigel, gelatin
- MeSH terms
- Breast Neoplasms, Cell Movement, Cell Survival, Female, Humans, Drug Delivery Systems, Spheroids, Cellular, Hyaluronan Receptors, Xanthones, Protein Kinase Inhibitors, Cell Proliferation, Hypoxia-Inducible Factor 1, alpha Subunit, Aptamers, Nucleotide, Nanoparticles, MCF-7 Cells
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