Prompt Description

Deep Proteomics-Discovered Molecular Identities Reveal Biological Functions of Nanoparticle Protein Corona Key Scientific Questions: 1. Missing Causal Mechanisms: How do the key physicochemical properties of nanoparticles (surface charge, PEGylation, morphology, material) systematically and causally determine their protein corona composition, and in turn, regulate biological fates such as cellular uptake and immune recognition? 2. Data Resource Bottleneck: How can we overcome the fragmentation and low quality of existing public proteomics data to establish a high-quality, standardized nanobio interaction database that can support reliable mechanism discovery and model prediction? Research Methods: This study employs an integrated "data mining-guided experimental construction" strategy. First, a literature-mined nanoparticle protein corona database (LM-NPC-DB) was constructed through text mining and literature data integration, systematically evaluating the field's research paradigm and data quality defects. Based on this analysis, a standardized nanoparticle library covering 42 different materials, charges, PEGylation states, and morphologies was rationally designed and synthesized. Subsequently, a high-quality in-house nanoparticle protein corona database (IH-NPC-DB) was constructed by strictly following uniform standard operating procedures. This database, with its high reproducibility, high protein coverage, and minimized missing values, serves as the core data foundation for this study. On this basis, combined with bioinformatics analysis (differential protein analysis, pathway enrichment, network analysis), machine learning models (predicting morphology-specific adsorption), and functional cell experiments (such as using gene knockout cell models to verify specific uptake pathways), the quantitative relationship between nanoparticle properties, protein corona composition, and biological effects was systematically decoded. Conclusions: This study is expected to establish and validate a clear causal framework of "nanoparticle properties → protein corona composition → biological fate." Specific conclusions include: 1. Surface charge guides protein adsorption through electrostatic-hydrophobic synergistic effects. Negatively charged particles enrich adhesion proteins and mediate efficient cell uptake via Itgav, while positively charged particles preferentially bind to apolipoproteins. 2. PEGylation actively reduces the adsorption of immune-related proteins such as complement/coagulation factors, reconstructing the protein corona to achieve "immune stealth" and effectively inhibit macrophage inflammatory responses. 3. Particle morphology shapes a unique protein adsorption fingerprint. Spherical particles enrich adhesion-related proteins, while rod-shaped particles exhibit high immunogenic potential, both achieved through different physical interactions and interfacial geometric effects. 4. Different materials exhibit complementary protein adsorption profiles, which can be used as "molecular amplifiers" to specifically enrich low-abundance disease biomarkers, providing a theoretical basis for constructing multi-material combined liquid biopsy panels. Ultimately, this study not only provides a standardized database (IH-NPC-DB) that surpasses the quality of existing public data, but also enables rational...