Journal: ACS Nano

Article Title: Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment

doi: 10.1021/acsnano.4c04814

Figure Lengend Snippet: Schematic design of PM&EM/JQ1 NP-mediated delivery of JQ1 to myofibroblast for the treatment of heart failure. (a) Schematic illustration of the preparation of PM&EM/JQ1 NPs. (b) Schematic diagram of intravenous injection of PM&EM/JQ1 NPs to the heart failure mice.

Article Snippet: JQ1, a chemical compound, was obtained from Selleck (USA).

Techniques: Injection

Journal: ACS Nano

Article Title: Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment

doi: 10.1021/acsnano.4c04814

Figure Lengend Snippet: Preparation and characterization of PM&EM/JQ1 NPs. (a) The lipid membrane is labeled with FRET dye for DiO and Dil and then fused with the platelet membrane. The fluorescence intensity was recorded. (b) The particle size was measured by dynamic light scattering (DLS) (mean ± SD, n = 3). (c) Zeta potential distribution (mean ± SD, n = 3 independent experiments) of platelet membrane vesicles, erythrocyte membrane vesicles, JQ1 NPs, and PM&EM/JQ1 NPs. (d) Representative TEM image of PM&EM/JQ1 NPs. Scale bar = 100 nm. (e) CLSM image of PM&EM/JQ1 NPs. Two membranes and a physical mixture of PLGA coated with DiI fluorescein were used as controls. Scale bar = 20 μm. (f) Principal component analysis (PCA) and the 2D score plots display repertoires of PM vesicles, EM vesicles, and PM&EM vesicles. Each point represents a sample, and ellipses represent 95% confidence regions (mean ± SD, n = 3 independent experiments). (g) Classification of PM&EM/JQ1 NPs proteins by the biological process. (h) Classification of PM&EM/JQ1 NP proteins by cellular component. (i) Heatmap of protein levels from PM&EM NPs, PM NPs, and EM NPs. (mean ± SD, n = 3). (j) Protein composition of PM&EM/JQ1 NPs was shown by SDS-PAGE analysis. (k) Analysis of PM&EM/JQ1 NPs through Western Blot to achieve targeting and immune evasion of key protein receptors.

Article Snippet: JQ1, a chemical compound, was obtained from Selleck (USA).

Techniques: Membrane, Labeling, Fluorescence, Zeta Potential Analyzer, SDS Page, Western Blot

Journal: ACS Nano

Article Title: Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment

doi: 10.1021/acsnano.4c04814

Figure Lengend Snippet: Targeted delivery and immune evasion performance of PM&EM/JQ1 NPs. (a) After 4h incubation with in vitro collagen, the ability of collagen to adhere to DiI NPs, PM&EM/JQ1 NPs, gray is collagen, red is encapsulated DiI fluorescent molecules, scale bar = 10 μm. (b) Fibroblasts and their collagen production stimulated by angiotensin II, green for type I collagen, blue for nuclei; scale bar = 20 μm. (c) After 4 h incubation of activated fibroblasts (stimulated with angiotensin II), cell adhesion, uptake of DiI nanoparticles, PM&EM/JQ1 NPs scale bar = 25 μm. (d) FC analysis of activated fibroblasts after 4 h incubation of DiI NPs, PM&EM/JQ1 NPs, and DiI-positive fibroblasts as a percentage of total fibroblasts (mean ± SD, n = 4 independent experiments). (e) RAW 264.7 cells were coincubated with DiI NPs and PM&EM/JQ1 NPs nanoparticles for 4 h and then subjected to laser confocal analysis, blue for nuclei, green for lysosomes, red for encapsulated DiI fluorescent molecules, scale bar = 25 μm. (f) DiI-positive macrophages as a percentage of total macrophages after coincubation with DiI-labeled nanoparticles for 4 h (mean ± SD, n = 3 independent experiments). *** p < 0.001, one-way ANOVA, Tukey’s multiple comparison test.

Article Snippet: JQ1, a chemical compound, was obtained from Selleck (USA).

Techniques: Incubation, In Vitro, Labeling, Comparison

Journal: ACS Nano

Article Title: Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment

doi: 10.1021/acsnano.4c04814

Figure Lengend Snippet: Potential mechanisms and therapeutic targets for PM treatment of myocardial infarction-induced cardiac fibrosis. (a) Volcano plots show the differentially expressed genes (DEGs) between the PM&EM/JQ1 NPs and free JQ1 in bulk RNA-seq data sets. (b) Top five upregulated (red) and downregulated (green) KEGG pathways by normalized enrichment score (NES) identified by GSEA in PM&EM/JQ1 NPs. (c) GSEA-based KEGG analysis of Oxidative phosphorylation. (d) GSEA-based KEGG analysis of the ECM-receptor interaction. (e) Heatmap showing the genes of Oxidative phosphorylation. Heatmap scale is a Z score. (f) Heatmap showing the genes of the Oxidative ECM-receptor interaction. Heatmap scale is a Z score. (g) Heatmap of BRD4- bound enhancers in free JQ1 and PM&EM/JQ1 NPs therapy heart covering 3kb upstream and downstream of the enhancer summit, where enhancers are grouped by increased or decreased BRD4 binding in PM&EM/JQ1 NPs therapy heart compared to free JQ1 therapy. (h) ATAC-seq from the fibrosis sites of MI mosue with free JQ1 and PM&EM/JQ1 NPs therapy at the Plcg1 locus. (i) Down-regulated pathway enrichment analysis of PM&EM/JQ1 NPs therapy relative to Free JQ1 in ATACseq.

Article Snippet: JQ1, a chemical compound, was obtained from Selleck (USA).

Techniques: Biomarker Discovery, RNA Sequencing, Phospho-proteomics, Binding Assay

Journal: ACS Nano

Article Title: Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment

doi: 10.1021/acsnano.4c04814

Figure Lengend Snippet: Biosafety analysis of JQ1, JQ1 NPs and PM&EM/JQ1 NPs. (a) Representative cross section from liver and kidney stained with H&E and intestines with Alcian blue, scale bar = 100 μm. (b) Venn diagrams of JQ1, nephrotoxicity, gastrointestinal toxicity, and hepatoxicity related gene from GENCARDS. (c) GO pathway enrichment analysis (biological process, BP) of the common gene from different groups. (d) Immunofluorescence staining of mitochondria (Mito, red) and reactive oxygen species (ROS, green) in the kidney and liver. Nuclei were counterstained with DAPI (blue); scale bar = 20 μm.

Article Snippet: JQ1, a chemical compound, was obtained from Selleck (USA).

Techniques: Staining, Immunofluorescence