Figure 3 Schematic representation of PS-QD micelles and evaluation of their targeting efficacy. Uptake of PS-QD micelles by J774A.1 macrophages was tested as a function of micelle size and PS coverage. The uptake was highest for PS (100) and minimal for PS (50). Next, the PEG packing density of PS (50) micelles
was controlled by tuning the homogenization speed of the micro-emulsion that resulted in the preparation of micelles of two different sizes of approximately 40-nm PS (50-1) and approximately 100-nm PS (50-2) micelles. When tested for macrophage-specific targeting, it was found that PS (50-1) micelles with a size of approximately buy JPH203 40 nm were not uptaken by macrophages (incubated at 25 pM) and
Combretastatin A4 datasheet at different micelle concentrations (Additional file 1: Figure S6), while PS (50-2) micelles with a size of approximately 100 nm in size are avidly uptaken by macrophages (MFI 15.1 versus 5.6) (Figure 2B). Further, the possibility that the uptake of larger-sized PS (50-2) micelles by macrophages were indeed correlated to the surface coverage of PS in the micelles and independent of surface negative charge was also investigated. For this purpose, the amount of PS in the PS (50-2) micelles was varied by substituting PS with a negatively charged lipid: 1,2-dipalmitoyl-sn-glycero-3-phospho-(glycerol) (DPPG) at two PS-DPPG molar ratios (40:10 and 30:20) but keeping the overall molar ratio constant at 50 mol%). As shown in Figure 2C, PS-PG (40:10) micelles containing more PS than PS-PG (30:20) micelles were taken up to a higher degree by macrophages, suggesting macrophage
uptake of micelles was dependent on the PS content in micelles and independent of the surface charge. The above results show that PEG coverage and size can be fine-tuned to influence the surface exposure of PS and thus permit or block the ligand receptor SAHA HDAC recognition and cell uptake. Conclusions In conclusion, a size-dependent uptake of approximately 100-nm PS-QD micelles that resemble dead/apoptotic cells and recognized as ‘self’ are detected and uptaken by macrophage-like cells, whereas PS-QD micelles that are intermediate in size (approximately 40 nm) and recognized as ‘non-self’ are not uptaken by Resminostat macrophage-like cells. The importance of this study based on the size and phospholipid coating of equal molar ratio of PS and PL-PEG for nanoparticles can be further extended to targeted delivery of inorganic particles for imaging or drug delivery applications. Acknowledgements We deeply thank Dr. Patrick Kee for helpful discussions through the work and in preparation of this manuscript. This work is supported by National Institutes of Health (NIH), National Heart Lung Blood Institute (NHLBI) R21Grant (Grant # 8226385). Dr. Maiseyeu was supported by American Heart Association NCRP Scientist Development Grant 13SDG14500015.