Journal of microencapsulation · 2025
Synergistic effect of DR5-targeted capsules loaded with doxorubicin in drug-resistant 3D tumour spheroids.
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Trushina Daria, Gileva Anastasia, Yagolovich Anne, Gasparian Marine, Kurbanova Leyli, Burov Sergey, Bukreeva Tatiana, Pallaeva Tatiana, Artemov Vladimir, Oleinikov Vladimir, Markvicheva Elena
Аннотация
AIM: To develop polyelectrolyte multilayer capsules (PMC) loaded with doxorubicin (DOX) and modified with the DR5-B protein to overcome drug resistance in MCF-7 breast cancer cells.
METHODS: The capsules were prepared by layer-by-layer (LbL) assembly followed by thermal shrinking, DOX encapsulation and DR5-B surface modification. The capsules were characterised using scanning electron microscopy (SEM), dynamic light scattering (DLS), and UV-Vis spectrophotometry. Cellular uptake was assessed by confocal microscopy, flow cytometry, and fluorimetry. Cytotoxicity was evaluated by MTT-test in 2D and 3D in vitro models.
RESULTS: Mean capsule size was 320 ± 90 nm (PDI 0.39), mean ζ-potential was +29 ± 5 mV. The encapsulation efficiencies (ЕЕ) of DOX and DR5-B were 85 ± 7% and 80 ± 4%, with loading capacities (LC) of 9 ± 2 w/w% and 145 ± 40 w/w%, respectively. Shrunken capsules exhibited 3.5-fold higher internalisation than non-shrunken ones. DR5-B increased capsule accumulation by 1.8-fold. The capsules showed synergistic cytotoxicity in DR5-B-resistant MCF-7 spheroids (IC50 227 ± 13 ng/mL), being non-toxic to fibroblasts.
METHODS: The capsules were prepared by layer-by-layer (LbL) assembly followed by thermal shrinking, DOX encapsulation and DR5-B surface modification. The capsules were characterised using scanning electron microscopy (SEM), dynamic light scattering (DLS), and UV-Vis spectrophotometry. Cellular uptake was assessed by confocal microscopy, flow cytometry, and fluorimetry. Cytotoxicity was evaluated by MTT-test in 2D and 3D in vitro models.
RESULTS: Mean capsule size was 320 ± 90 nm (PDI 0.39), mean ζ-potential was +29 ± 5 mV. The encapsulation efficiencies (ЕЕ) of DOX and DR5-B were 85 ± 7% and 80 ± 4%, with loading capacities (LC) of 9 ± 2 w/w% and 145 ± 40 w/w%, respectively. Shrunken capsules exhibited 3.5-fold higher internalisation than non-shrunken ones. DR5-B increased capsule accumulation by 1.8-fold. The capsules showed synergistic cytotoxicity in DR5-B-resistant MCF-7 spheroids (IC50 227 ± 13 ng/mL), being non-toxic to fibroblasts.