Fig. 4: Nanoparticles can overcome BTZ resistance by using receptor-mediated endocytosis. | Blood Cancer Journal

Fig. 4: Nanoparticles can overcome BTZ resistance by using receptor-mediated endocytosis.

From: BCMA-targeted bortezomib nanotherapy improves therapeutic efficacy, overcomes resistance, and modulates the immune microenvironment in multiple myeloma

Fig. 4

A Schematic representation of (a) free BTZ cellular uptake by simple diffusion and immediate efflux out by PgP pump. (b) When PgP pump is blocked by verapamil, then free BTZ stays in cytosol. (c) Nanoparticulated drug delivery system avoids PgP-mediated drug efflux. Inhibition of chymotryptic activity was measured after treatment with BTZ, BTZ-NPs, and BCMA-BTZ-NPs in BTZ-sensitive B MM.1S and C H929 cells, as well as BTZ-resistant D RPMI-8226 Dox-40 cells. Cytotoxicity was measured on E BTZ-sensitive RPMI-8226 and F BTZ-resistant RPMI-8226 Dox-40 myeloma cell lines after treatment with PgP inhibitor verapamil, alone and in combination with BTZ and BTZ nanoparticles. G Confocal images of MM.1S cells (Upper panel) and H929 (Lower panel) showing co-localization of nanoparticles with early endosomes. Mean ± SD of 2-5 independent experiments performed in triplicate, ns not significant, ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05, significance determined by Student’s t-test.

Back to article page