Effect of bortezomib-loaded anti-CD38 chitosan NPs on drug resistance. A) The effect of vehicle (control), BTZ as a free drug (5 nM), empty chitosan NPs, non-targeted chitosan NPs loaded with BTZ equivalent amounts to 5 nM, and anti-CD38 chitosan NPs loaded with BTZ equivalent amounts to 5 nM for 48 h on: A) cell adhesion-mediated drug resistance in co-culture with MSP-1 (myeloma-derived stroma); and B) hypoxia-mediated drug resistance, *p<0.05. C) The effect of vehicle (control), BTZ as a free drug (10 nM), empty chitosan NPs, non-targeted chitosan NPs loaded with BTZ equivalent amounts to 10 nM, and anti-CD38 chitosan NPs loaded with BTZ equivalent amounts to 10 nM for 48 h on survival of MM cells cultured in 3DTEBM, *p<0.05. D) Confocal microscopy images of MM cells cultured (green) in 3DTEBM after 24h treatment with AF633 anti-CD38 chitosan NPs (red), shown by a Z-Stack rotated view, and images at different depths of the z-stack to show the co-localization (white arrows) of NPs and MM cells in yellow; Scale bar= 50 μm.