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. Author manuscript; available in PMC: 2024 Dec 13.
Published in final edited form as: Nano Lett. 2023 Nov 22;23(23):10971–10982. doi: 10.1021/acs.nanolett.3c03222

Figure 4. Intravenously injected PLGA-b-HA nanoparticles localize to the hippocampi of both aged APP/PS1 mice and their control littermates but not young adult mice.

Figure 4.

(A) Coronal brain cryosections were immunostained for Aβ and counterstained with nuclear marker Hoechst 33342. Extracellular senile Aβ plaques were observed in all areas of the hippocampi of aged APP/PS1 mice (13–16-month-old), but not in the age-matched non-carrier (NC) mice (13–16-month-old) or young APP/PS1, NC control, and C57BL/6J mice (3–5-month-old). Confocal z-stack images (an optical section of 1.0 μm) were collected from the CA1, CA3, and Dente gyrus (DG) regions of the hippocampus and shown as representative images. Image size: 640.17 μm x 640.17 μm. Scale bar: 100μm. (B) Young adult APP/PS1, NC control littermates, and C57BL/6J mice (3–5 mo old), and aged APP/PS1 mice and their NC control littermates (13–17 mo old) received an i.v. injection of saline or PLGA-b-HA particles encapsulating AF488-conjugated BSA (16 mg / kg) via their tail veins. After 2 h, mice were subjected to transcardial perfusion of PBS followed by fixation with 2% PFA. Cryoprotected brain tissues were sectioned to 30 μm coronal sections and counterstained with nuclear marker Hoechst 33342. Confocal images (an optical section of 1.0 μm) were collected from the CA1, CA3, and Dente gyrus (DG) regions of the hippocampus. Image size: 62.68 μm x 62.68 μm x 1.0 μm. Scale: each inset square is 10 μm x 10 μm. (C) Quantification of the average number of particles. Data represents the mean ± SEM. Particles are counted when artificial unit (AU) intensity is 5 standard deviations above the mean intensity for each image using the ThunderStorm plug-in with ImageJ. Sample size in CA1 (z-stack images and particle-injected mice): n = 12 from 3 aged APP/PS1 mice, n = 13 from 3 aged NC mice, n = 22 from 3 adult APP/PS1 mice, n = 12 from 3 adult NC mice, and n = 13 from 3 adult C57BL/6J mice. Sample size in CA3 (z-stack images and particle-injected mice): n = 13 from 3 aged APP/PS1 mice, n = 16 from 3 aged NC mice, n = 15 from 3 adult APP/PS1 mice, n = 12 from 2 adult NC mice, n = 12 from 3 adult C57BL/6J mice. Sample size in DG (z-stack images and particle-injected mice): n = 11 from 3 aged APP/PS1 mice, n = 15 from 3 aged NC mice, n = 16 from 3 adult APP/PS1 mice, n = 13 from 2 adult NC mice, and n = 12 from 3 adult C57BL/6J mice. Sample size of images analyzed for saline-injected mice: CA1 = 13, CA3 = 13, and DG = 12 from 3 adult C57BL/6J mice. One-way ANOVA with Tukey Post Hoc test results are shown (*p<0.05; **p<0.01; ***p<0.001).