Highly Biocompatible Zwitterionic Phospholipids Coated Upconversion Nanoparticles for Efficient Bioimaging

The potential of upconversion nanoparticles (UCNPs) in various biomedical applications, including immunoassays, biomedical imaging, and molecular sensing, requires their surface derivatized to be hydrophilic and biocompatible. Here, a new family of compact zwitterionic ligand systems composed with functional phospholipids was designed and used for the surface modification of UCNPs. The zwitterionic UCNPs are hydrophilic, compact, and easily functionalized. It was proved that zwitterionic phospholipids could provide UCNPs with not only extended pH and salt stability but also little nonspecific interactions to positively and negatively charged proteins, low nonspecific adhesion in live-cell imaging process. Most notably, the efficient in vivo tumor imaging performance and long blood circulation half-life suggests the excellent biocompatibility for in vivo imaging of the zwitterionic UCNPs

Programmed Nanoreactors Boost Immune Response through ROS Cascade Amplification along with RNS Storm

High oxidative stress plays a significant role in activating intracellular signaling pathways that govern immunogenic cell death (ICD). Nevertheless, immune response is often confined by limited reactive oxygen species (ROS) production, upregulated antioxidant defense, and an immunosuppressive tumor microenvironment. Herein, the GSH/pH-sensitive Mn2+/polydopamine-incorporated hollow mesoporous tetrasulfide-bridged organosilica nanoreactors loaded with l-arginine (l-Arg) were successfully constructed (A@MnHMONs-PEG). Under near-infrared light (NIR) illumination, the programmed nanoreactors directly generate a large amount of ROS via “Mn2+-based Fenton-like catalysis and tetrasulfide bridge-mediated GSH depletion” for photothermal-intensified chemodynamic therapy, meanwhile ROS could oxidize the guanidine groups of l-Arg to produce nitric oxide (NO) for gas therapy. Moreover, both photothermal and massive ROS substantially induce cancer immune responses by up-regulating ICD. Furthermore, the more powerful peroxynitrite anion (ONOO–) is sequentially generated through the interaction of ROS and NO. It could polarize macrophages from M2 into M1 phenotype to reverse immunosuppression and enhance immune response. In vivo experiments conclusively prove that our programmed nanoreactors could combine photothermal-chemodynamic-NO therapy and concurrently enhance immune response via ROS cascade amplification along with ONOO– storm for elimination of the primary tumor and inhibition of recurrence/metastasis. Our programmed nanoreactors open up new paths for improving the anticancer immune response

Signaling pathway analysis in symptomatic late-onset FECD.

<p>(A) Top 25 significantly different pathways were selected according to DEGs in FECD. (B) PPI of genes which appeared more than 10 times in significantly different pathways. Some important pathways in this study were labeled on it. (C) Signaling pathway network was plotted according to KEGG database.</p

The summary of the dataset GSE74123.

<p>(A) The cluster heatmap of GSE74123. (B) The PCA of GSE74123 showed that significant differences between the two groups of samples. (C) Pearson heatmap showed the correlation between the two groups of samples. There was a high correlation within each group of samples. (D) The volcano plot showed the distribution of all genes by fold change and P value. The expression of FECD group was compared with control group. Genes with |log2 (fold change) | > 1 and P value < 0.05 were selected as the DEGs.</p

Heatmaps of four major types of genes.

<p>(A) Senescence, (B) ECM, (C) EMT, (D) visual perception and (E) immune response related DEGs were picked and normalized by Z-score. Red represents up-regulated expression. Blue represents up-regulated expression.</p

Pathological molecular mechanism of symptomatic late-onset Fuchs endothelial corneal dystrophy by bioinformatic analysis

<div><p>Fuchs endothelial corneal dystrophy (FECD) is a degenerative disease characterized by corneal endothelial decompensation. FECD causes corneal stromal and epithelial edema and progressively develops into bullous keratopathy, which can eventually lead to blindness. However, the exact pathogenesis is unknown. In this study, we performed an in-depth bioinformatic analysis of the dataset GSE74123 to determine the differentially expressed genes (DEGs) of symptomatic late-onset FECD compared with a normal control. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the pathological molecular mechanism of FECD. We found that cell senescence, reactive oxygen species (ROS), the extracellular matrix (ECM), epithelial-mesenchymal transition (EMT) and immune response-related genes play an important role in the pathological development of symptomatic late-onset FECD. In addition, we revealed that down-regulated IL-6, enhanced NF-κB activity and a suite of orchestrated chemokine responses induce fibrocyte differentiation from monocyte to dendritic cell maturation. PI3K plays a key role in the molecular mechanism of symptomatic late-onset FECD. This study enhances our understanding of the molecular mechanism of FECD pathogenesis and will improve the diagnostics and therapy of FECD patients in the future.</p></div

The biological process (BP) in GO enrichment of DEGs.

<p>(A) The top 25 significantly up-regulated BP GO terms in FECD group. (B) The top 25 significantly down-regulated BP GO terms in FECD group.</p

Additional file 1 of Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy

Supplementary Material

The schematic diagram of possible pathological and molecular mechanisms of symptomatic late-onset FECD.

<p>In the symptomatic late-onset of FECD, corneal stroma is cloudy. DM becomes thick. Corneal guttae appear. The density of CECs is decreased. CECs lose their hexagonal shape. The reason for these phenomena is that the expression of cell senescence, EMT, ECM and immune response related genes changes.</p