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 M
Bonafè, Francesca, Claudia Pazzini, Silvia Marchionni, Carlo Guarnieri, and Claudio Muscari. "Complete Disaggregation of MCF-7-derived Breast Tumour Spheroids with Very Low Concentrations of α-Mangostin Loaded in CD44 Thioaptamer-tagged Nanoparticles." International journal of medical sciences 16, no. 1 (2019): 33.