ABSTRACT
Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.
Subject(s)
Biocompatible Materials , Materials Testing , Mesenchymal Stem Cells , Nanoparticles , Particle Size , Silicon Dioxide , Surface Properties , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacology , Nanoparticles/chemistry , Animals , Rats , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Survival/drug effects , Cells, Cultured , Osteogenesis/drug effectsABSTRACT
BACKGROUND: To explore the role of intestinal flora in seborrhea, non-targeted metabolomics analysis was carried out. METHODS: Fecal samples were collected from 5 seborrheic patients and 5 healthy controls from October 2019 to April 2020. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to detect metabolic fingerprinting in feces samples, and high-throughput sequencing and bioinformatic analysis of 16S rRNA for intestinal flora. The variable importance in projection (VIP) values of orthogonal partial least squares-discriminant analysis (OPLS-DA) and P values of univariate statistical analysis were used to determine the differential metabolites between the seborrhea group and the control group. The interaction between flora and metabolites was analyzed using several approaches. RESULTS: A total of 45 metabolites with significantly different intensities were found between the seborrhea group and the healthy control group. A positive correlation between flora and metabolites was found in 57 pairs and a negative correlation was found in 104 pairs. In addition, 11 metabolic pathways were significantly altered, including 4 amino acid metabolic pathways, 2 bile acid metabolic pathways, and 2 basic metabolic signaling pathways (ABC transporters pathway and mTOR signaling pathway). Central carbon metabolism in cancer, glutathione metabolism, protein digestion and absorption were also involved. CONCLUSIONS: The occurrence of seborrhea may be related to changes in intestinal flora and metabolic pathways. There is a close association between seborrhea and amino acid metabolic pathways or ABC transporters.
