The objective of this study was to fabricate dasatinib-loaded nanoparticles and evaluate their efficacy in inhibiting cellular processes of the retinal pigment epithelium (RPE) related to proliferative vitreoretinopathy (PVR), for which there are no approved pharmacological approaches. We successfully encapsulated dasatinib, a poorly soluble multi-targeted tyrosine kinase inhibitor which has great potential for the treatment of PVR, into nanoparticles prepared from micellation of PEG-b-PCL. The size of the nanomicelles was approximately 55nm with a narrow distribution. They increased the solubility of dasatinib by 475× and provided a sustained drug release. ARPE-19, an immortal RPE cell line, was used to assess the in vitro efficacy of micellar dasatinib because the RPE is believed to play a key role in the pathogenesis of PVR. Three cell-based assays, namely, proliferation, adhesion and migration, which represent three important PVR-related cellular changes of the RPE, were conducted and the cytotoxicity of micelles was also evaluated. Both blank and dasatinib-loaded micelles were non-cytotoxic towards ARPE-19 cells. Micellar dasatinib significantly inhibited cell proliferation, adhesion and migration compared to the free drug; this might be attributable to enhanced solubility. PEG-b-PCL micelles were taken up into the ARPE-19 cells by an energy-dependent clatharin and caveolae-mediated endocytosis. Our results indicated that cellular uptake and the anti-proliferation effect of drugloaded micelles were linearly correlated. Drug loading appears to be a critical parameter for cellular uptake which in turn impacts the in vitro bioactivities of polymeric micelles. Our results clearly demonstrated that dasatinib-encapsulated micelles offer considerable promise in the management of PVR.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.colsurfb.2015.12.053 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma.
Nat Commun
December 2024
Laboratory of Cellular Biophysics, The Rockefeller University, New York, NY, USA.
Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FLC pathogenesis and the relationships among FLC, FLC-like, and other liver tumors, we performed a massive multi-omics analysis.
View Article and Find Full Text PDFNS1 binding protein regulates stress granule dynamics and clearance by inhibiting p62 ubiquitination.
Nat Commun
December 2024
Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University, Daejeon, Korea.
The NS1 binding protein, known for interacting with the influenza A virus protein, is involved in RNA processing, cancer, and nerve cell growth regulation. However, its role in stress response independent of viral infections remains unclear. This study investigates NS1 binding protein's function in regulating stress granules during oxidative stress through interactions with GABARAP subfamily proteins.
View Article and Find Full Text PDFUnsupervised inter-domain transformation for virtually stained high-resolution mid-infrared photoacoustic microscopy using explainable deep learning.
Nat Commun
December 2024
Department of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Mid-infrared photoacoustic microscopy can capture biochemical information without staining. However, the long mid-infrared optical wavelengths make the spatial resolution of photoacoustic microscopy significantly poorer than that of conventional confocal fluorescence microscopy. Here, we demonstrate an explainable deep learning-based unsupervised inter-domain transformation of low-resolution unlabeled mid-infrared photoacoustic microscopy images into confocal-like virtually fluorescence-stained high-resolution images.
View Article and Find Full Text PDFMultivariate stochastic modeling for transcriptional dynamics with cell-specific latent time using SDEvelo.
Nat Commun
December 2024
School of Data Science, The Chinese University of Hong Kong-Shenzhen, Shenzhen, China.
Recently, RNA velocity has driven a paradigmatic change in single-cell RNA sequencing (scRNA-seq) studies, allowing the reconstruction and prediction of directed trajectories in cell differentiation and state transitions. Most existing methods of dynamic modeling use ordinary differential equations (ODE) for individual genes without applying multivariate approaches. However, this modeling strategy inadequately captures the intrinsically stochastic nature of transcriptional dynamics governed by a cell-specific latent time across multiple genes, potentially leading to erroneous results.
View Article and Find Full Text PDFDefects in hair cells disrupt the development of auditory peripheral circuitry.
Nat Commun
December 2024
The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Deafness is the most common form of sensory impairment in humans and frequently caused by defects in hair cells of the inner ear. Here we demonstrate that in male mice which model recessive non-syndromic deafness (DFNB6), inactivation of Tmie in hair cells disrupts gene expression in the neurons that innervate them. This includes genes regulating axonal pathfinding and synaptogenesis, two processes that are disrupted in the inner ear of the mutant mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!