ABSTRACT
The molecular heterogeneity of extracellular vesicles (EVs) and the co-isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single-EV and particle (siEVP) protein and RNA assay (siEVP PRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVP PRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single-particle resolution, the siEVP PRA outperformed the sensitivities of bulk-analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex biofluids, EVs from various glioma cell lines were processed with small RNA sequencing, whereby two mRNAs and two miRNAs associated with glioblastoma multiforme (GBM) were chosen for cross-validation. Despite the presence of single-EV-LP co-isolates in serum, the siEVP PRA detected GBM-associated vesicular RNA profiles in GBM patient siEVPs. The siEVP PRA effectively examines intravesicular, intervesicular, and interparticle heterogeneity with diagnostic promise.
Subject(s)
Extracellular Vesicles , Glioblastoma , MicroRNAs , Humans , Extracellular Vesicles/genetics , Extracellular Vesicles/metabolism , Lipopolysaccharides , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger , Lipoproteins , Glioblastoma/diagnosis , Glioblastoma/geneticsABSTRACT
Persistent perfluorinated compounds (PFCs) have been recognized as a global environmental issue. Developing methods without leading to additional burden in nature will be essential for PFCs removal. Herein, we functionalized iron nanoparticles on living diatom (Dt) to efficiently enable the Fenton reaction and reactive oxygen species (ROS) production. Iron nanoparticles at the surface of living diatom act as promising catalytic agents to trigger OH radical generation from H2O2. Dt plays dual roles: i) as solid support for effective adsorption, and ii) it supplies oxygen and inherently produces ROS under stress conditions, which improves removal efficiency of PFCs. We also demonstrated its reusability by simple magnetic separation and 85% of decomposition efficiency could still be achieved. This newly developed diatom-assisted bioremediation strategy enables green and efficient PFC decomposition and shall be readily applicable to other persistent pollutants.
Subject(s)
Alkanesulfonic Acids/isolation & purification , Bioreactors , Caprylates/isolation & purification , Diatoms , Fluorocarbons/isolation & purification , Magnetic Iron Oxide Nanoparticles/chemistry , Environmental Pollutants/isolation & purificationABSTRACT
Silica-based materials have extensive biomedical applications owing to their unique physical, chemical, and biological properties. Recently, increasing studies have examined the mechanisms involved in biosilicification to develop novel, fine-tunable, eco-friendly materials and/or technologies. In this review, we focus on recent developments in bio-templated silica synthesis and relevant applications in drug delivery systems, tissue engineering, and biosensing.
Subject(s)
Biosensing Techniques/methods , Drug Delivery Systems/methods , Silanes/chemistry , Silicon Dioxide/chemistry , Tissue Engineering/methods , Animals , DNA/chemistry , Diatoms/chemistry , Flagella/chemistry , Flagella/ultrastructure , Humans , Mice , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Nanotubes/chemistry , Nanotubes/ultrastructure , Peptides/chemistry , Polysaccharides/chemistryABSTRACT
Novel therapeutics is urgently needed to prevent cancer-related deaths. MicroRNAs that act as tumor suppressors have been recognized as a next-generation tumor therapy, and the restoration of tumor-suppressive microRNAs using microRNA replacements or mimics may be a less toxic, more effective strategy due to fewer off-target effects. Here, we designed the novel multifunctional oligonucleotide nanocarrier complex composed of a tumor-targeting aptamer sequence specific to mucin 1 (MUC1), poly-cytosine region for fluorescent silver nanocluster (AgNC) synthesis, and complimentary sequence for microRNA miR-34a loading. MiR-34a was employed because of its therapeutic effect of inhibiting oncogene expression and inducing apoptosis in carcinomas. By monitoring the intrinsic fluorescence of AgNC, it was clearly shown that the constructed complex (MUC1-AgNCm-miR-34a) enters MCF-7 cells. To evaluate the efficacy of this nanocarrier for microRNA delivery, we investigated the gene and protein expression levels of downstream miR-34a targets (BCL-2, CDK6, and CCND1) by quantitative PCR and western blotting, respectively, and the results indicated their effective inhibition by miR-34a. This novel multifunctional AgNC-based nanocarrier can aid in improving the efficacy of breast cancer theranostics.
Subject(s)
Nanoparticles/chemistry , Oligonucleotides/chemistry , Silver/chemistry , Aptamers, Nucleotide/genetics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Gene Silencing/physiology , Gene Transfer Techniques , Humans , MCF-7 Cells , MicroRNAs/administration & dosage , MicroRNAs/chemistry , Mucin-1/genetics , Oligonucleotides/administration & dosageABSTRACT
Carbon-based nanomaterials serve as a type of smart material for photo-triggered disease theranostics. The inherent physicochemical properties of these nanomaterials facilitate their use for less invasive treatments. This review summarizes the properties and applications of materials including fullerene, nanotubes, nanohorns, nanodots and nanographenes for photodynamic nanomedicine in cancer and antimicrobial therapies. Carbon nanomaterials themselves do not usually act as photodynamic therapy (PDT) agents owing to the high hydrophobicity, however, when the surface is passivated or functionalized, these materials become great vehicles for PDT. Moreover, conjugation of carbonaceous nanomaterials with the photosensitizer (PS) and relevant targeting ligands enhances properties such as selectivity, stability, and high quantum yield, making them readily available for versatile biomedical applications.
