Self-propelled enzyme-controlled IR-mesoporous silica Janus nanomotor for smart delivery.

Here, we report the preparation of a novel Janus nanoparticle with opposite Ir and mesoporous silica nanoparticles through a partial surface masking with toposelective modification method. This nanomaterial was employed to construct an enzyme-powered nanomachine with self-propulsion properties for on-command delivery. The cargo-loaded nanoparticle was provided with a pH-sensitive gate and unit control at the mesoporous face by first attaching boronic acid residues and further immobilization of glucose oxidase through reversible boronic acid esters with the carbohydrate residues of the glycoenzyme. Addition of glucose leads to the enzymatic production of H2O2 and gluconic acid, being the first compound catalytically decomposed at the Ir nanoparticle face producing O2 and causing the nanomachine propulsion. Gluconic acid leads to a pH reduction at the nanomachine microenvironment causing the disruption of the gating mechanism with the subsequent cargo release. This work demonstrates that enzyme-mediated self-propulsion improved release efficiency being this nanomotor successfully employed for the smart release of Doxorubicin in HeLa cancer cells.

Mitigation of acrylamide formation in wood oven baked pizza base using wholemeal and refined wheat flour with low free asparagine content: considerations on fibre intake and starch digestibility.

BACKGROUND: In wheat-derived bakery products, the quantity of free asparagine (fAsn) has been identified as a key factor in acrylamide (AA) formation. Based on this assumption, four varieties of common wheat (Triticum aestivum L.), Stromboli, Montecarlo, Sothys and Cosmic, selected for their different fAsn content inside the grain, were studied to evaluate their potential in the production of pizza with reduced AA levels. To this purpose, wholemeal and refined flours were obtained from each variety. RESULTS: The fAsn content ranged from 0.25 to 3.30 mmol kg-1, with higher values for wholemeal flours which also showed greater amount of ash, fibre and damaged starch than refined wheat flours. All types of flours were separately used to produce wood oven baked pizza base, according to the Traditional Speciality Guaranteed EU Regulation (97/2010). AA reduction in the range 47-68% was found for all the selected wheat cultivars, compared with a commercial flour, with significantly lower values registered when refined flour was used. Moreover, refined leavened dough samples showed decreased levels of fAsn and reducing sugars due to the fermentation activity of yeasts. Furthermore, it was confirmed that pizza made with wholemeal flours exhibited lower rapidly digestible starch (RDS) and rapidly available glucose (RAG) values compared to that prepared with the refined flour. CONCLUSION: This study clearly shows that a reduced asparagine content in wheat flour is a key factor in the mitigation of AA formation in pizza base. Unfortunately, at the same time, it is highlighted how it is necessary to sacrifice the beneficial effects of fibre intake, such as lowering the glycaemic index, in order to reduce AA. © 2024 Society of Chemical Industry.

An intercommunicated nanosystem for dual delivery.

Here, we describe the design of a novel particle-to-particle intercommunicated nanosystem for dual delivery, triggered by physical and chemical inputs. The nanosystem was composed of an Au-mesoporous silica Janus nanoparticle loaded with paracetamol, mechanized with light-sensitive supramolecular gates at the mesoporous face and functionalized on the metal surface with the enzyme acetylcholinesterase. The second component was a mesoporous silica nanoparticle loaded with rhodamine B and gated with thiol-sensitive ensembles. Upon irradiation of this nanosystem with a near-UV light laser, an analgesic drug was released from the Janus nanomachine due to disassembling of the photosensitive gating mechanism. Further addition of N-acetylthiocholine leads to the enzymatic production of thiocholine at the Janus nanomachine, thus acting as a "chemical messenger" causing the disruption of the gating mechanism at the second mesoporous silica nanoparticle with the subsequent dye release.

Electrochemical aptasensor based on anisotropically modified (Janus-type) gold nanoparticles for determination of C-reactive protein.

Novel Janus nanoparticles based on Au colloids anisotropically modified with polyamidoamine dendrons were prepared though a masking/toposelective modification approach. These nanomaterials were further functionalized with horseradish peroxidase on the dendritic face and provided on the opposite metal surface with a ssDNA aptamer for C-reactive protein (CRP). The resulting nanoparticles were employed as biorecognition/signaling elements to construct an amperometric aptasensor with sandwich-type architecture for the specific detection of this cardiac biomarker. To do this, screen-printed carbon electrodes modified with electrodeposited Au nanoparticles and functionalized with anti-CRP aptamers were used as transduction interface. The aptasensor was employed for the amperometric detection of CRP (working potential: - 200 mV vs pseudo-Ag/AgCl) in the broad range from 10 pg·mL-1 to 1.0 ng·mL-1 with a detection limit of 3.1 pg·mL-1. This electroanalytical device also showed good specificity, reproducibility (RSD = 9.8%, n = 10), and stability and was useful to quantify CRP in reconstituted human serum samples, with a RSD of 13.3%.

An enzyme-controlled mesoporous nanomachine for triple-responsive delivery.

The construction of a novel enzyme-controlled nanomachine with multiple release mechanisms for on-command delivery is described. This nanodevice was assembled by modifying mesoporous silica nanoparticles with 2-(benzo[d]thiazol-2-yl)phenyl 4-aminobenzoate moieties, and further capped with ß-cyclodextrin-modified glucose oxidase neoglycoenzyme. The device released the encapsulated payload in the presence of H2O2 and acidic media. The use of glucose as an input chemical signal also triggered cargo release through the enzymatic production of gluconic acid and hydrogen peroxide, and the subsequent disruption of the gating mechanism at the mesoporous surface. The nanodevice was successfully employed for the enzyme-controlled release of doxorubicin in HeLa cancer cells.

Supramolecular Enzymatic Labeling for Aptamer Switch-Based Electrochemical Biosensor.

Here we report a novel labeling strategy for electrochemical aptasensors based on enzymatic marking via supramolecular host-guest interactions. This approach relies on the use of an adamantane-modified target-responsive hairpin DNA aptamer as an affinity bioreceptor, and a neoglycoconjugate of ß-cyclodextin (CD) covalently attached to a redox enzyme as a labeling element. As a proof of concept, an amperometric aptasensor for a carcinoembryonic antigen was assembled on screen-printed carbon electrodes modified with electrodeposited fern-like gold nanoparticles/graphene oxide and, by using a horseradish peroxidase-CD neoglycoenzyme as a biocatalytic redox label. This aptasensor was able to detect the biomarker in the concentration range from 10 pg/mL to 1 ng/mL with a high selectivity and a low detection limit of 3.1 pg/mL in human serum samples.

A glutathione disulfide-sensitive Janus nanomachine controlled by an enzymatic AND logic gate for smart delivery.

This work describes the assembly of a novel enzyme-controlled nanomachine operated through an AND Boolean logic gate for on-command delivery. The nanodevice was constructed on Au-mesoporous silica Janus nanoparticles capped with a thiol-sensitive gate-like molecular ensemble on the mesoporous face and functionalized with glutathione reductase on the gold face. This autonomous nanomachine employed NADPH and glutathione disulfide as input chemical signals, leading to the enzymatic production of reduced glutathione that causes the disruption of the gating mechanism on the mesoporous face and the consequent payload release as an output signal. The nanodevice was successfully used for the autonomous release of doxorubicin in HeLa cancer cells and RAW 264.7 macrophage cells.

Sucrose-Responsive Intercommunicated Janus Nanoparticles Network.

Inspired by biological systems, the development of artificial nanoscale materials that communicate over a short distance is still at its early stages. This work shows a new example of a cooperating system with intercommunicated devices at the nanoscale. The system is based on the new sucrose-responsive Janus gold-mesoporous silica (Janus Au-MS) nanoparticles network with two enzyme-powered nanodevices. These nanodevices involve two enzymatic processes based on invertase and glucose oxidase, which are anchored on the Au surfaces of different Janus Au-MS nanoparticles, and N-acetyl-L-cysteine and [Ru(bpy)3]2+ loaded as chemical messengers, respectively. Sucrose acts as the INPUT, triggering the sequential delivery of two different cargoes through the enzymatic control. Nanoscale communication using abiotic nanodevices is a developing potential research field and may prompt several applications in different disciplines, such as nanomedicine.

Amperometric aptasensor with sandwich-type architecture for troponin I based on carboxyethylsilanetriol-modified graphene oxide coated electrodes.

A novel amperometric aptasensor for the specific detection of cardiac troponin I (cTnI) was constructed by using screen-printed carbon electrodes coated with a carboxyethylsilanetriol-modified graphene oxide derivative as transduction element. This novel carboxylic acid-enriched nanomaterial allows easy and high load immobilization of the capture aptamer molecules on the electrode surface. The biosensing interface was assembled by covalent attachment of an amino-functionalized DNA aptamer on the carboxylic acid-enriched electrode surface. The sensing approach relies on the specific recognition of cTnI by the aptamer and further assembly of a sandwich-type architecture with a novel aptamer-peroxidase conjugate as signaling element. The aptasensor was employed to detect the cardiac biomarker in the broad range from 1.0 pg/mL to 1.0 µg/mL with a detection limit of 0.6 pg/mL. This electroanalytical device also showed high specificity, reproducibility and stability, and was useful to quantify cTnI in reconstituted human serum samples.

Ultrafast Directional Janus Pt-Mesoporous Silica Nanomotors for Smart Drug Delivery.

Development of bioinspired nanomachines with an efficient propulsion and cargo-towing has attracted much attention in the last years due to their potential biosensing, diagnostics, and therapeutics applications. In this context, self-propelled synthetic nanomotors are promising carriers for intelligent and controlled release of therapeutic payloads. However, the implementation of this technology in real biomedical applications is still facing several challenges. Herein, we report the design, synthesis, and characterization of innovative multifunctional gated platinum-mesoporous silica nanomotors constituted of a propelling element (platinum nanodendrite face), a drug-loaded nanocontainer (mesoporous silica nanoparticle face), and a disulfide-containing oligo(ethylene glycol) chain (S-S-PEG) as a gating system. These Janus-type nanomotors present an ultrafast self-propelled motion due to the catalytic decomposition of low concentrations of hydrogen peroxide. Likewise, nanomotors exhibit a directional movement, which drives the engines toward biological targets, THP-1 cancer cells, as demonstrated using a microchip device that mimics penetration from capillary to postcapillary vessels. This fast and directional displacement facilitates the rapid cellular internalization and the on-demand specific release of a cytotoxic drug into the cytosol, due to the reduction of the disulfide bonds of the capping ensemble by intracellular glutathione levels. In the microchip device and in the absence of fuel, nanomotors are neither able to move directionally nor reach cancer cells and deliver their cargo, revealing that the fuel is required to get into inaccessible areas and to enhance nanoparticle internalization and drug release. Our proposed nanosystem shows many of the suitable characteristics for ideal biomedical destined nanomotors, such as rapid autonomous motion, versatility, and stimuli-responsive controlled drug release.

A 1-to-2 demultiplexer hybrid nanocarrier for cargo delivery and activation.

A biocomputing strategy implemented in hybrid nanocarriers for controlled cargo delivery is described. The nanodevice consists of enzyme-functionalized Janus Au-mesoporous silica nanoparticles, which behave as an electronic demultiplexer (DEMUX). The nanocarrier is capable of reading molecular information from the environment (lactose) and selecting one of two possible outputs (galactose production or 4-methylumbellilferone release and activation) depending on the presence of an addressing input (NAD+).

An enzyme-controlled Janus nanomachine for on-command dual and sequential release.

A novel nanomachine for dual and sequential delivery of two different compounds was developed by grafting a thiol group and a pH sensitive ß-cyclodextrin-based gate-like ensemble on acetylcholinesterase-modified Au-mesoporous silica Janus nanoparticles.

Electrochemical biosensors based on nucleic acid aptamers.

During recent decades, nucleic acid aptamers have emerged as powerful biological recognition elements for electrochemical affinity biosensors. These bioreceptors emulate or improve on antibody-based biosensors because of their excellent characteristics as bioreceptors, including limitless selection capacity for a large variety of analytes, easy and cost-effective production, high stability and reproducibility, simple chemical modification, stable and oriented immobilization on electrode surfaces, enhanced target affinity and selectivity, and possibility to design them in target-sensitive 3D folded structures. This review provides an overview of the state of the art of electrochemical aptasensor technology, focusing on novel aptamer-based electroanalytical assay configurations and providing examples to illustrate the different possibilities. Future prospects for this technology are also discussed. Graphical abstract.

A chemical circular communication network at the nanoscale.

In nature, coordinated communication between different entities enables a group to accomplish sophisticated functionalities that go beyond those carried out by individual agents. The possibility of programming and developing coordinated communication networks at the nanoscale-based on the exchange of chemical messengers-may open new approaches in biomedical and communication areas. Here, a stimulus-responsive circular model of communication between three nanodevices based on enzyme-functionalized Janus Au-mesoporous silica capped nanoparticles is presented. The output in the community of nanoparticles is only observed after a hierarchically programmed flow of chemical information between the members.

Dendrimers as Soft Nanomaterials for Electrochemical Immunosensors.

Electrochemical immunosensors are antibody-based affinity biosensors with a high impact on clinical, environmental, food, and pharmaceutical analysis. In general, the analytical performance of these devices is critically determined by the materials and reagents used for their construction, signal production and amplification. Dendrimers are monodisperse and highly branched polymers with three-dimensional structures widely employed as "soft" nanomaterials in electrochemical immunosensor technology. This review provides an overview on the state-of-the-art in dendrimer-based electrochemical immunosensors, focusing on those using polyamidoamine and poly (propylene imine) dendrimers. Special emphasis is given to the most original methods recently reported for the construction of immunosensor architectures incorporating dendrimers, as well as to novel sensing approaches based on dendrimer-assisted signal enhancement strategies.

Stimulus-responsive nanomotors based on gated enzyme-powered Janus Au-mesoporous silica nanoparticles for enhanced cargo delivery.

Here we report functional stimulus-responsive nanomotors based on Janus Au-mesoporous silica nanoparticles capable of self-propelling via the biocatalytic conversion of chemical fuel, that read information from the environment (the presence of glutathione) and accordingly deliver a cargo.

Enzyme-Powered Gated Mesoporous Silica Nanomotors for On-Command Intracellular Payload Delivery.

The introduction of stimuli-responsive cargo release capabilities on self-propelled micro- and nanomotors holds enormous potential in a number of applications in the biomedical field. Herein, we report the preparation of mesoporous silica nanoparticles gated with pH-responsive supramolecular nanovalves and equipped with urease enzymes which act as chemical engines to power the nanomotors. The nanoparticles are loaded with different cargo molecules ([Ru(bpy)3]Cl2 (bpy = 2,2'-bipyridine) or doxorubicin), grafted with benzimidazole groups on the outer surface, and capped by the formation of inclusion complexes between benzimidazole and cyclodextrin-modified urease. The nanomotor exhibits enhanced Brownian motion in the presence of urea. Moreover, no cargo is released at neutral pH, even in the presence of the biofuel urea, due to the blockage of the pores by the bulky benzimidazole:cyclodextrin-urease caps. Cargo delivery is only triggered on-command at acidic pH due to the protonation of benzimidazole groups, the dethreading of the supramolecular nanovalves, and the subsequent uncapping of the nanoparticles. Studies with HeLa cells indicate that the presence of biofuel urea enhances nanoparticle internalization and both [Ru(bpy)3]Cl2 or doxorubicin intracellular release due to the acidity of lysosomal compartments. Gated enzyme-powered nanomotors shown here display some of the requirements for ideal drug delivery carriers such as the capacity to self-propel and the ability to "sense" the environment and deliver the payload on demand in response to predefined stimuli.

An Interactive Model of Communication between Abiotic Nanodevices and Microorganisms.

The construction of communication models at the micro-/nanoscale involving abiotic nanodevices and living organisms has the potential to open a wide range of applications in biomedical and communication technologies. However, this area remains almost unexplored. Herein, we report, as a proof of concept, a stimuli-responsive interactive paradigm of communication between yeasts (as a model microorganism) and enzyme-controlled Janus Au-mesoporous silica nanoparticles. In the presence of the stimulus, the information flows from the microorganism to the nanodevice, and then returns from the nanodevice to the microorganism as a feedback.

Janus nanocarrier powered by bi-enzymatic cascade system for smart delivery.

We report herein the assembly of an integrated nanodevice with bi-enzymatic cascade control for on-command cargo release. This nanocarrier is based on Au-mesoporous silica Janus nanoparticles capped at the mesoporous face with benzimidazole/ß-cyclodextrin-glucose oxidase pH-sensitive gate-like ensembles and functionalized with invertase on the gold face. The rationale for this delivery mechanism is based on the invertase-mediated hydrolysis of sucrose yielding glucose, which is further transformed into gluconic acid by glucose oxidase causing the disruption of the pH-sensitive supramolecular gates at the Janus nanoparticles. This enzyme-powered device was successfully employed in the autonomous and on-demand delivery of doxorubicin in HeLa cancer cells.

Janus Gold Nanostars-Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery.

Janus gold nanostar-mesoporous silica nanoparticle (AuNSt-MSNP) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule (5), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton-responsive benzimidazole-ß-cyclodextrin supramolecular gatekeepers (N 1). Upon irradiation with NIR-light, the photolabile compound 5 photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR-light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non-cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability.