Exploring and exploiting the synergy of non-covalent interactions on the surface of gold nanoparticles for fluorescent turn-on sensing of bacterial lipopolysaccharide

National Natural Science Foundation of China [21075101]; National Basic Research Program of China [2011CB910403]; Planned Science and Technology Project of Xiamen, China [3502z20113006]; Specialized Research Fund for the Doctoral Program of Higher Education of China [200803840007]; NFFTBS [J1030415]The sensing of lipopolysaccharide (LPS) relies on the synergy of multiple electrostatic and hydrophobic interactions between LPS and the sensor. However, how non-covalent interactions are coordinated to impel the recognition process still remains elusive, and the exploration of which would promote the development of LPS sensors with higher specificity and sensitivity. In this work, we hypothesize that Au NPs would provide a straightforward and flexible platform for studying the synergy of non-covalent interactions. The detailed mechanism of interactions between the designed fluorescent probes and Au NPs with two distinct surface properties was systematically explored. We demonstrated that only when the electrostatic attraction and hydrophobic stacking are both present, the binding of fluorescent probes onto Au NPs can be not only highly efficient, but also positively cooperative. After that, hybrid systems that consist of Au NPs and surface-assembled fluorescent probes were exploited for fluorescent turn-on sensing of LPS. The results show that the sensitivity and selectivity to LPS relies strongly on the binding affinity between fluorescent probes and Au NPs. Fluorescent probes assembled Au NPs thus provide an attractive platform for further optimization of the sensitivity/selectivity of LPS sensing

Deciphering the synthetic and refolding strategy of a cysteine-rich domain in the tumor necrosis factor receptor (TNF-R) for racemic crystallography analysis and d-peptide ligand discovery

Many cell-surface receptors are promising targets for chemical synthesis because of their critical roles in disease development. This synthetic approach enables investigations by racemic protein crystallography and ligand discovery by mirror-image methodologies. However, due to their complex nature, the chemical synthesis of a receptor can be a significant challenge. Here, we describe the chemical synthesis and folding of a central, cysteine-rich domain of the cell-surface receptor tumor necrosis factor 1 which is integral to binding of the cytokine TNF-α, namely, TNFR-1 CRD2. Racemic protein crystallography at 1.4 Å confirmed that the native binding conformation was preserved, and TNFR-1 CRD2 maintained its capacity to bind to TNF-α (KD ≈ 7 nM). Encouraged by this discovery, we carried out mirror-image phage display using the enantiomeric receptor mimic and identified a d-peptide ligand for TNFR-1 CRD2 (KD = 1 μM). This work demonstrated that cysteine-rich domains, including the central domains, can be chemically synthesized and used as mimics for investigations

Light-responsive nanogated ensemble based on polymer grafted mesoporous silica hybrid nanoparticles

Mesoporous silica nanoparticles grafted with light-responsive polymer on the outer surface were developed as novel nanogated ensembles, which allow encapsulation and release of drug and biological molecules under light irradiation.National Natural Science Foundation of China [20875079, 20835005]; Planned Science and Technology Project of Xiamen, China [3502z20080011]; Specialized Research Fund for the Doctoral Program of Higher Education of China [200803840007

Molecule-scale controlled-release system based on light-responsive silica nanoparticles

We report a molecule-scale controlled-release system based on silica nanoparticles bearing a photoactive o-nitrobenzyl bromide linkage, which allows cage and release of drug or biologically active molecules by light

Light-triggered covalent assembly of gold nanoparticles in aqueous solution

UV light irradiation triggers Au NPs that are respectively functionalized on the surface by o-nitrobenzyl alcohol and benzylamine to proceed with a covalent ligation reaction, which leads to assembling of Au NPs into anisotropic one-dimensional (1D) arrays in aqueous solution via indazolone linkages.National Natural Science Foundation of China[20875079, 20835005]; The Planned Science and Technology Project of Xiamen, China[3502z20080011]; Specialized Research Fund for Doctoral Program of Higher Education of China[200803840007

A facile and general approach for the synthesis of fluorescent silica nanoparticles doped with inert dyes

A general and facile approach was developed for the synthesis of almost monodisperse fluorescent silica nanoparticles (NPs) doped with inert dyes, which are organic fluorophores that are strongly fluorescent but are hydrophobic or lack a covalent binding group. The prepared NPs were mesoporous and the dye molecules were encapsulated in the pores via hydrophobic interaction with the CTAB template. The NPs were stable and highly fluorescent in aqueous solution, and have potential applications in bioanalysis and fluorescence encoding.National Natural Science Foundation of China[20875079, 20835005]; Planned Science and Technology Project of Xiamen, China[3502z20080011]; Specialized Research Fund for the Doctoral Program of Higher Education of China[200803840007

Condensation of 2-((Alkylthio)(aryl)methylene)malononitrile with 1,2-Aminothiol as a novel bioorthogonal reaction for site-specific protein modification and peptide cyclization

Site-specific modification of peptides and proteins has wide applications in probing and perturbing biological systems. Herein we report that 1,2-aminothiol can react rapidly, specifically and efficiently with 2-((alkylthio)(aryl)methylene)malononitrile (TAMM) under biocompatible conditions. This reaction undergoes a unique mechanism involving thiol-vinyl sulfide exchange, cyclization, and elimination of dicyanomethanide to form 2-aryl-4,5-dihydrothiazole (ADT) as a stable product. An 1,2-aminothiol functionality can be introduced into a peptide or a protein as an N-terminal cysteine or an unnatural amino acid. The bioorthogonality of this reaction was demonstrated by site-specific labeling of not only synthetic peptides and a purified recombinant protein but also proteins on mammalian cells and phages. Unlike other reagents in bioorthogonal reactions, the chemical and physical properties of TAMM can be easily tuned. TAMM can also be applied to generate phage-based ADT-cyclic peptide libraries without reducing phage infectivity. Using this approach, we identified ADT-cyclic peptides with high affinity to different protein targets, providing valuable tools for biological studies and potential therapeutics. Furthermore, the mild reaction conditions of TAMM condensation warrant its use with other bioorthogonal reactions to simultaneously achieve multiple site-specific modifications

Fluorescent core-shell silica nanoparticles as tunable precursors: towards encoding and multifunctional nano-probes

Core-shell silica nanoparticles comprised of a RuBpy doped silica core and a Pas-DTPA doped silica shell were synthesized and post-functionalized with an encoding fluorescence combination and multiplex imaging function

GPX8 regulates pan-apoptosis in gliomas to promote microglial migration and mediate immunotherapy responses

IntroductionGliomas have emerged as the predominant brain tumor type in recent decades, yet the exploration of non-apoptotic cell death regulated by the pan-optosome complex, known as pan-apoptosis, remains largely unexplored in this context. This study aims to illuminate the molecular properties of pan-apoptosis-related genes in glioma patients, classifying them and developing a signature using machine learning techniques.MethodsThe prognostic significance, mutation features, immunological characteristics, and pharmaceutical prediction performance of this signature were comprehensively investigated. Furthermore, GPX8, a gene of interest, was extensively examined for its prognostic value, immunological characteristics, medication prediction performance, and immunotherapy prediction potential. ResultsExperimental techniques such as CCK-8, Transwell, and EdU investigations revealed that GPX8 acts as a tumor accelerator in gliomas. At the single-cell RNA sequencing level, GPX8 appeared to facilitate cell contact between tumor cells and macrophages, potentially enhancing microglial migration. ConclusionsThe incorporation of pan-apoptosis-related features shows promising potential for clinical applications in predicting tumor progression and advancing immunotherapeutic strategies. However, further in vitro and in vivo investigations are necessary to validate the tumorigenic and immunogenic processes associated with GPX8 in gliomas