Biology subjects

Coreas, R.

Publications and source records attributed to Coreas, R..

3 recordsLinked to original sources

bioRxiv2025

Protein corona formed on lipid nanoparticles compromises delivery efficiency of mRNA cargo

Lipid nanoparticles (LNPs) are the most clinically advanced nonviral RNA-delivery vehicles, though challenges remain in fully understanding how LNPs interact with biological systems. In vivo, proteins form an associated corona on LNPs that redefines their physicochemical properties and influences delivery outcomes. Despite its importance, the LNP protein corona is challenging to study owing to the technical difficulty of selectively recovering soft nanoparticles from biological samples. Herein, we developed a quantitative, label-free mass spectrometry-based proteomics approach to characterize the protein corona on LNPs. Critically, this protein corona isolation workflow avoids artifacts introduced by the presence of endogenous nanoparticles in human biofluids. We applied continuous density gradient ultracentrifugation for protein-LNP complex isolation, with mass spectrometry for protein identification normalized to protein composition in the biofluid alone. With this approach, we quantify proteins consistently enriched in the LNP corona including vitronectin, C-reactive protein, and alpha-2-macroglobulin. We explore the impact of these corona proteins on cell uptake and mRNA expression in HepG2 human liver cells, and find that, surprisingly, increased levels of cell uptake do not correlate with increased mRNA expression in part likely due to protein corona-induced lysosomal trafficking of LNPs. Our results underscore the need to consider the protein corona in the design of LNP-based therapeutics. Abstract Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=58 SRC="FIGDIR/small/633942v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@2fef29org.highwire.dtl.DTLVardef@fe7613org.highwire.dtl.DTLVardef@1f9de01org.highwire.dtl.DTLVardef@15e5237_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Deep profiling of plant stress biomarkers following bacterial pathogen infection with protein corona based nano-omics

Detection and remediation of stress in crops is vital to ensure agricultural productivity. Conventional forms of assessing stress in plants are limited by feasibility, delayed phenotypic responses, inadequate specificity, and lack of sensitivity during initial phases of stress. While mass spectrometry is remarkably precise and achieves high-resolution, complex samples, such as plant tissues, require time-consuming and biased depletion strategies to effectively identify low-abundant stress biomarkers. Here, we bypassed these reduction methods via a nano-omics approach, where gold nanoparticles were used to enrich time- and temperature-dependent stress-related proteins through biomolecular corona formation that were subsequently analyzed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). This nano-omic approach was more effective than a conventional proteomic analysis using UHPLC- MS/MS for resolving biotic-stress induced responses at early stages of pathogen infection in Arabidopsis thaliana, well before the development of visible phenotypic symptoms, as well as in distal tissues of pathogen infected plants at early timepoints. The enhanced sensitivity of this nano-omic approach enables the identification of stress-related proteins at early critical timepoints, providing a more nuanced understanding of plant-pathogen interactions that can be leveraged for the development of early intervention strategies for sustainable agriculture.

plant biology↗

bioRxiv2024

AI-based Prediction of Protein Corona Composition on DNA Nanostructures

DNA nanotechnology has emerged as a powerful approach to engineering biophysical tools, therapeutics, and diagnostics because it enables the construction of designer nanoscale structures with high programmability. Based on DNA base pairing rules, nanostructure size, shape, surface functionality, and structural reconfiguration can be programmed with a degree of spatial, temporal, and energetic precision that is difficult to achieve with other methods. However, the properties and structure of DNA constructs are greatly altered in vivo due to spontaneous protein adsorption from biofluids. These adsorbed proteins, referred to as the protein corona, remain challenging to control or predict, and subsequently, their functionality and fate in vivo are difficult to engineer. To address these challenges, we prepared a library of diverse DNA nanostructures and investigated the relationship between their design features and the composition of their protein corona. We identified protein characteristics important for their adsorption to DNA nanostructures and developed a machine-learning model that predicts which proteins will be enriched on a DNA nanostructure based on the DNA structures design features and protein properties. Our work will help to understand and program the function of DNA nanostructures in vivo for biophysical and biomedical applications.

bioengineering↗