19F NMR ON/OFF nanoparticles: a universal approach for the specific detection of DNA-binding cancer biomarkers.

A supramolecular approach for the design of assembly-disassembly-driven 19F ON/OFF nanoparticles, triggered by specific molecular recognition, for the detection of DNA binding cancer biomarkers is reported. The key to our design strategy is the characteristic 19F NMR signal of the probe, which completely vanishes in the aggregated state due to the shortening of T2 relaxation. However, molecular recognition of DNA by the cancer biomarkers through specific molecular recognition results in the disassembly of the nanoparticles, which causes the restoration of the characteristic 19F signal of the probe. The universal nature of the approach is demonstrated through the selective detection of various cancer biomarkers including miRNA, ATP, thrombin, and telomerase.

Multisite Labeling of Proteins Using the Ligand-Directed Reactivity of Triggerable Michael Acceptors.

Targeted modification of endogenous proteins without genetic manipulation of protein expression machinery has a range of applications from chemical biology to drug discovery. Despite being demonstrated to be effective in various applications, target-specific protein labeling using ligand-directed strategies is limited by stringent amino acid selectivity. Here, we present highly reactive ligand-directed triggerable Michael acceptors (LD-TMAcs) that feature rapid protein labeling. Unlike previous approaches, the unique reactivity of LD-TMAcs enables multiple modifications on a single target protein, effectively mapping the ligand binding site. This capability is attributed to the tunable reactivity of TMAcs that enable the labeling of several amino acid functionalities via a binding-induced increase in local concentration while remaining fully dormant in the absence of protein binding. We demonstrate the target selectivity of these molecules in cell lysates using carbonic anhydrase as the model protein. Furthermore, we demonstrate the utility of this method by selectively labeling membrane-bound carbonic anhydrase XII in live cells. We envision that the unique features of LD-TMAcs will find use in target identification, investigation of binding/allosteric sites, and studying membrane proteins.

Optical Fingerprinting of Dynamic Interfacial Reaction Pathways Using Liquid Crystals.

Reactions at interfaces between fluid phases are widely used to synthesize small molecules, polymers, and nanoparticles. In situ monitoring of the underlying dynamic reaction pathways remains challenging. Liquid crystals (LCs) have been used to detect simple chemical transformations at interfaces in situations where interface-bound reactants and products trigger distinct equilibrium orientations of LCs. However, whether or not LCs can be used to report complex reaction pathways via nonequilibrium states generated by reactions has not been explored. Here we explore this question using SN2' nucleophilic substitution reactions that involve a synthetic amphiphile and a series of amine-based nucleophiles with one to four reaction sites. Although all reactants and products generate the same equilibrium LC orientation, we find that each nucleophile defines a distinct set of possible reaction pathways with a characteristic spatial and temporal LC optical response unique to the nucleophile. Additional experiments reveal that the nonequilibrium orientational states of the LCs arise from a combination of dynamic interfacial processes that include adsorption/desorption of reactants, the presence of reaction intermediates on the LC interface, and the generation of interfacial tension gradients (Marangoni stresses). Overall, our results reveal that the spatiotemporal optical outputs of LCs ("optical fingerprints") can be a rich source of information regarding interfacial reactions.

Core Hydrophobicity of Supramolecular Nanoparticles Induces NLRP3 Inflammasome Activation.

Designer nanomaterials capable of delivering immunomodulators to specific immune cells have been extensively studied. However, emerging evidence suggests that several of these nanomaterials can nonspecifically activate NLRP3 inflammasomes, an intracellular multiprotein complex controlling various immune cell functions, leading to undesirable effects. To understand what nanoparticle attributes activate inflammasomes, we designed a multiparametric polymer supramolecular nanoparticle system to modulate various surface and core nanoparticle-associated molecular patterns (NAMPs), one at a time. We also investigated several underlying signaling pathways, including lysosomal rupture-cathepsin B maturation and calcium flux-mitochondrial ROS production, to gain mechanistic insights into NAMPs-mediated inflammasome activation. Here, we report that out of the four NAMPs tested, core hydrophobicity strongly activates and positively correlates with the NLRP3 assembly compared to surface charge, core rigidity, and surface hydrophobicity. Moreover, we demonstrate different signaling inclinations and kinetics followed by differential core hydrophobicity patterns with the most hydrophobic ones exhibiting both lysosomal rupture and calcium influx early on. Altogether, this study will help design the next generation of polymeric nanomaterials for specific regulation of inflammasome activation, aiding efficient immunotherapy and vaccine delivery.

Galactose Grafted Two-Dimensional Nanosheets as a Scaffold for the In Situ Synthesis of Silver Nanoparticles: A Potential Catalyst for the Reduction of Nitroaromatics.

Two major hurdles in NP-based catalysis are the aggregation of the NPs and their recycling. Immobilization of NPs onto a 2D support is the most promising strategy to overcome these difficulties. Herein, amphiphilicity-driven self-assembly of galactose-hexaphenylbenzene-based amphiphiles into galactose-decorated 2D nanosheet is reported. The extremely dense decoration of reducing sugar on the surface of the sheets is used for the in situ synthesis and immobilization of ultrafine catalytically active AgNPs by using Tollens' reaction. The potential of the system as a catalyst for the reduction of various nitroaromatics is demonstrated. Enhanced catalytic activity is observed for the immobilized AgNPs when compared to the corresponding discrete AgNPs. Recovery of the catalytic system from the reaction mixture by ultrafiltration and its subsequent recycling for several cycles without dropping its activity is shown. This is the first report demonstrating the in situ synthesis and immobilization of ultrafine AgNPs onto a 2D nanosheet that exhibits excellent catalytic performance for the reduction of nitroaromatics.

Galactose-Grafted 2D Nanosheets from the Self-Assembly of Amphiphilic Janus Dendrimers for the Capture and Agglutination of Escherichia coli.

High aspect ratio, sugar-decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate-based Janus amphiphiles that spontaneously self-assemble into high aspect ratio 2D sheets are reported. The unique structural features of the sheets include the extremely high aspect ratio and dense display of galactose on the surface. These structural characteristics allow the sheet to act as a supramolecular 2D platform for the capture and agglutination of E. coli through specific multivalent noncovalent interactions, which significantly reduces the mobility of the bacteria and leads to the inhibition of their proliferation. Our results suggest that the design strategy demonstrated here can be applied as a general approach for the crafting of biomolecule-decorated 2D nanosheets, which can perform as 2D platforms for their interaction with specific targets.