Nanoimmunotherapy production scale-up and evaluation in Apoe−/− mice

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Presentation transcript:

Fig. 1 Nanoimmunotherapy production scale-up and evaluation in Apoe−/− mice. Nanoimmunotherapy production scale-up and evaluation in Apoe−/− mice. (A) Schematic of S-HDL production by high-pressure microfluidic homogenization. Transmission electron microscopy (TEM) image of S-HDL. Scale bar, 25 nm. (B) Schematic of radiolabeling of S-HDL with 89Zr by incorporating the phospholipid chelator DSPE-DFO in the formulation. (C) Blood time-activity curve for [89Zr]-S-HDL intravenously injected in Apoe−/− mice (n = 4; 12 weeks on Western diet). ID, injected dose. (D) Representative 3D-rendered PET/CT fusion image of an Apoe−/− mouse 26 hours after injection of [89Zr]-S-HDL. (E) Quantitation of tissue radioactivity distribution 26 hours after injection of [89Zr]-S-HDL in Apoe−/− mice (n = 4; 12 weeks on Western diet). On the right, representative autoradiograph showing radioactivity distribution on the aorta of an Apoe−/− mouse 26 hours after injection of [89Zr]-S-HDL. (F) Gating procedure used in the flow cytometry evaluation of microfluidizer-produced DiO-S-HDL’s cell specificity in Apoe−/− mouse aortas. (G) DiO mean fluorescence intensity (MFI) in different cell types from Apoe−/− mouse aortas. Control, uninjected animal. (H) Gating procedure used in the flow cytometry analysis to evaluate S-HDL treatment efficacy in aortas of Apoe−/− mice. (I) Quantitation of aortic macrophages (MØ) and monocytes (Ly6Chi Mo) after treatment with PBS (placebo) or S-HDL in Apoe−/− mice (n = 10 per group; 12 weeks on Western diet). (J) Representative aortic sections from Apoe−/− mice (n = 2 per group; 12 weeks on Western diet) treated with PBS (placebo) or S-HDL. Scale bars, 200 μm. CD68 is expressed on macrophages. aq., aqueous; Li, liver; Sp, spleen; Ki, kidney; LN, lymph node; Leu, leukocyte; Lin+, lineage positive; Neu, neutrophil. Data are presented as means ± SD from one experiment. *P < 0.05 (Mann-Whitney test). Tina Binderup et al., Sci Transl Med 2019;11:eaaw7736 Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works