Multiple myeloma (MM) is an incurable neoplasm characterized by infiltration of malignant plasma cells (PCs). Recently, the tumor microenvironment has become of great interest in MM as it known to be involved in progression and metastasis of the disease. CD24, is an adhesion molecule expressed during B cell maturation, is down regulated through the cells differentiation into PCs. Though the role of CD24 in solid cancers is well defined, its role in MM remains unknown. We aimed to understand the involvement of CD24 in MM by up-regulating its expression on MM cell lines by co-culturing the cells with bone marrow stromal cell (BMSCs). We then studied the differences between CD24+ and CD24− MM cells and found that CD24+ MM cells presented a less tumorigenic phenotype by impaired capability to migrate and to create colonies as compared with CD24− MM cells. Furthermore, there were significantly more apoptotic cells in the CD24+ fraction. Additionally, the CD24+ cells also upregulated CXCR4 expression. The decrease tumorigenicity correlated with a “more normal” PC immunophenotype in patients with MM and correlated with CD45 expression and a stronger expression of CXCR4. In summary, we found the expression of CD24 on PCs to correlate with attenuated tumorigenicity.

Local inflammation of the endothelium is associated with a plethora of cardiovascular diseases. Vascular-targeted carriers (VTCs) have been advocated to provide focal effective therapeutics to these disease sites. Here, we examine the design of functionalized nanoparticles (NPs) as VTCs that can specifically localize at an inflamed vessel wall under pathological levels of high shear stress, associated for example with clinical (or in vivo) conditions of vascular narrowing and arteriogenesis. To test this, carboxylated fluorescent 200 nm polystyrene particles were functionalized with ligands to activated endothelium, that is, an E-selectin binding peptide (Esbp), an anti ICAM-1 antibody, or using a combination of both. The functionalized NPs were investigated in vitro using microfluidic models lined with inflamed (TNF-α stimulated) and control endothelial cells (EC).Specifically, their adhesion was monitored under different relevant wall shear stresses (i.e., 40-300 dyne/cm 2 ) via real-time confocal microscopy. Experiments reveal a significantly higher specific adhesion of the examined functionalized NPs to activated EC for the window of examined wall shear stresses. Moreover, particle adhesion correlated with the surface coating density whereby under high surface coating (i.e.,~10,000 molecule/particle), shear-dependent particle adhesion increased significantly. Altogether, our results show that functionalized NPs can be designed to target inflamed endothelial cells under high shear stress. Such VTCs underscore the potential for attractive avenues in targeting drugs to vasoconstriction and arteriogenesis sites. K E Y W O R D S drug delivery, endothelium, inflammation, microfluidics, shear stress, vascular-targeted carriers (VTCs)

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