Fig. 3: Functional dendrisomes enhance uptake by breast CSCs in vitro and accumulation in breast tumor in mice.

a Fold increase in cellular uptake by breast cancer stem cells. **P < 0.01; (a) free coumarin-6; (b) dendrisomes carrying coumarin-6; (c) functional dendrisomes carrying coumarin-6. The data are presented as mean ± standard deviation (n = 3). The results indicate that the functional dendrisomes significantly enhance the cellular uptake by human cancer stem cells. b Cellular uptake mechanism of functional dendrisomes in MCF-7 CSCs. The results reveal that the endocytosis of functional dendrisomes are mainly mediated by caveolin and clathrin ferry, showing an energy-dependent process. c Colocalization of functional dendrisomes with lysosomes of MCF-7 CSCs (left) and SK-BR-3 CSCs (right) after endocytosis. The results indicate that the functional dendrisomes are less accumulated in lysosomes as compared with regular dendrisomes. d Schematic illustration of cellular uptake and mechanism of functional dendriomes carrying ATRA and DTX. e Penetrating ability and uptake of functional dendrisomes in MCF-7 CSCs spheres (left) and in SK-BR-3 CSCs spheres (right). The results demonstrate that both functional dendrisomes and regular dendrisomes are able to penetrate into the core of CSC spheres. f Accumulation of functional dendrisomes into tumor tissues in breast cancer-bearing mice. f1, in vivo real-time imaging; f2, ex vivo imaging. 1, free DiR, a fluorescent probe; 2, regular dendrisomes carrying DiR; 3, functional dendrisomes carrying DiR