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.

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.

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.

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.

Glucose-Responsive Enzyme-Controlled Mesoporous Nanomachine with a Layer-by-Layer Supramolecular Architecture.

Here we describe the construction of an integrated and pH-sensitive nanomachine with layer-by-layer supramolecular design and enzymatic control for on-command delivery. The nanodevice comprises a first layer of ß-cyclodextrin-coated gold nanoparticles as capping element of benzimidazole functionalized mesoporous silica nanoparticles, and a second control layer based on an adatamantane-modified glucose oxidase derivative. The nanomachine was selectively fuelled by glucose and successfully employed for the autonomous release of doxorubicin in HeLa cancer cells.

Hybrid Decorated Core@Shell Janus Nanoparticles as a Flexible Platform for Targeted Multimodal Molecular Bioimaging of Cancer.

In the recent years, targeted cancer theranosis, the concomitant therapeutic treatment and selective visualization of cancerous tissue, has become a powerful strategy to improve patient prognosis. In this context, targeted multimodal molecular imaging, the combination of different imaging modalities overcoming their individual limitations, has attracted great attention. Due to their unique properties, advanced nanomaterials have taken center stage in the development of theranostics. In this work, we report a novel Janus nanoplatform by combining an Fe3O4 NPs/mesoporous silica core@shell face together with an Au nanoparticle face. Due to its anisotropy, this hybrid nanomaterial enabled the orthogonal site-selective modification of each face permitting the incorporation of a targeting peptide for cancer detection (cRGD) and a fluorescent dye. Due to the intrinsic characteristics of this Janus nanoplatform together with those selectively generated on their surfaces, the resulting hybrid nanocarrier successfully promoted the in vivo tumor-targeted multimodal imaging by magnetic resonance (Fe3O4 core), computed tomography (AuNP face), and fluorescent tracking (fluorescent dye loading) in a fibrosarcoma-bearing mouse model. The achieved results endorse these hybrid Janus nanoparticles as a powerful and flexible platform with integrated imaging and carrier functionalities to be equipped with therapeutic features to generate an advanced multifunctional nanocarrier for targeted cancer theranosis.

Interactive models of communication at the nanoscale using nanoparticles that talk to one another.

'Communication' between abiotic nanoscale chemical systems is an almost-unexplored field with enormous potential. Here we show the design and preparation of a chemical communication system based on enzyme-powered Janus nanoparticles, which mimics an interactive model of communication. Cargo delivery from one nanoparticle is governed by the biunivocal communication with another nanoparticle, which involves two enzymatic processes and the interchange of chemical messengers. The conceptual idea of establishing communication between nanodevices opens the opportunity to develop complex nanoscale systems capable of sharing information and cooperating.

Enzyme-Controlled Nanodevice for Acetylcholine-Triggered Cargo Delivery Based on Janus Au-Mesoporous Silica Nanoparticles.

This work reports a new gated nanodevice for acetylcholine-triggered cargo delivery. We prepared and characterized Janus Au-mesoporous silica nanoparticles functionalized with acetylcholinesterase on the Au face and with supramolecular ß-cyclodextrin:benzimidazole inclusion complexes as caps on the mesoporous silica face. The nanodevice is able to selectively deliver the cargo in the presence of acetylcholine via enzyme-mediated acetylcholine hydrolysis, locally lowering the pH and opening the supramolecular gate. Given the key role played by ACh and its relation with Parkinson's disease and other nervous system diseases, we believe that these findings could help design new therapeutic strategies.

Gold nanoparticles-decorated silver-bipyridine nanobelts for the construction of mediatorless hydrogen peroxide biosensor.

Au nanoparticles modified with 4-mercaptopyridine and 6-mercapto-1-hexanol were used as coordination agents to prepare a novel hybrid nanomaterial with Ag:4,4'-bipyridine nanobelts. This nanohybrid was employed to modify glassy carbon electrodes and to construct a horseradish peroxidase-based mediatorless amperometric biosensor for H2O2. The electrode, poised at -100mV, exhibited a rapid response within 4s and a linear calibration range from 90pM to 6.5nM H2O2. The biosensor showed a high sensitivity of 283A/Mcm(2) and a very low detection limit of 45pM at a signal-to-noise ratio of 3. The enzyme biosensor showed high stability when stored at 4°C under dry conditions, retaining over 96% and 78% of its initial activity after 15 and 30days of storage at 4°C, respectively.

Novel reduced graphene oxide-glycol chitosan nanohybrid for the assembly of an amperometric enzyme biosensor for phenols.

A novel water-soluble graphene derivative was prepared from graphene oxide via a two-step modification approach. Graphene oxide was first functionalised with reactive epoxy groups by covalent modification with (3-glycidyloxypropyl)trimethoxysilane and further cross-linked with glycol chitosan. This graphene derivative was characterized using different microscopy and physicochemical methods and employed as a coating material for a glassy carbon electrode. The nanostructured surface was used as a support for the covalent immobilization of the enzyme laccase through cross-linking with glutaraldehyde. The enzyme electrode was tested for the amperometric detection of different phenolic compounds, which displayed excellent analytical behaviour toward catechol with a linear range of response from 200 nM to 15 µM, sensitivity of 93 mA M(-1) cm(-2), and low detection limit of 76 nM. The enzyme biosensor showed high stability when stored at 4 °C under dry conditions and was successfully employed to quantify the total phenolic compounds in commercial herbal tea samples.

Neoglycoenzyme-Gated Mesoporous Silica Nanoparticles: Toward the Design of Nanodevices for Pulsatile Programmed Sequential Delivery.

We report herein the design of a stimulus-programmed pulsatile delivery system for sequential cargo release based on the use of a lactose-modified esterase as a capping agent in phenylboronic acid functionalized mesoporous silica nanoparticles. The dual-release mechanism was based on the distinct stability of the cyclic boronic acid esters formed with lactose residues and the long naturally occurring glycosylation chains in the modified neoglycoenzyme. Cargo delivery in succession was achieved using glucose and ethyl butyrate as triggers.

Decorating graphene oxide/nanogold with dextran-based polymer brushes for the construction of ultrasensitive electrochemical enzyme biosensors.

A novel strategy was employed to prepare a water-soluble graphene derivative by using dextran-based polymer brushes as solubilizing agents. Graphene oxide was grafted with (3-mercaptopropyl) trimethoxysilane and further decorated with Au nanoparticles. This hybrid nanomaterial was then reduced and anchored with polysaccharide-based polymer brushes by chemisorption of an end-group thiolated dextran derivative on the Au nanoparticles. The resulting hybrid nonmaterial allowed highly stable aqueous dispersions to be obtained, which were used to coat glassy carbon electrodes for the preparation of a model tyrosinase electrochemical biosensor for catechol. The enzyme electrode showed excellent electroanalytical performance with fast response in about 5 s, a linear range of 100 pM-120 nM, a very high sensitivity of 45.9 A M-1 and a very low detection limit of 40 pM for catechol.

Nanochannel-based electrochemical assay for transglutaminase activity.

A novel electrochemical assay to quantify transglutaminase activity is reported. The assay is based on the enzyme-controlled diffusion of Fe(CN)6(3-/4-) through amino-functionalized nanochannels of a mesoporous silica thin film on a Au surface in the presence of N-benzyloxycarbonyl-L-glutaminylglycine.

Toward the design of smart delivery systems controlled by integrated enzyme-based biocomputing ensembles.

We report herein the design of a smart delivery system in which cargo delivery from capped mesoporous silica (MS) nanoparticles is controlled by an integrated enzyme-based "control unit". The system consists of Janus-type nanoparticles having opposing Au and MS faces, functionalized with a pH-responsive ß-cyclodextrin-based supramolecular nanovalve on the MS surface and two effectors, glucose oxidase and esterase, immobilized on the Au face. The nanodevice behaves as an enzymatic logical OR operator which is selectively fueled by the presence of D-glucose and ethyl butyrate.

Seed-mediated growth of jack-shaped gold nanoparticles from cyclodextrin-coated gold nanospheres.

Branched gold nanoparticles were prepared by a seed-mediated approach using per-6-thio-6-deoxy-ß-cyclodextrin capped gold nanospheres as seeds and a growth medium similar to those commonly employed to prepare gold nanorods, containing AgNO3, ascorbic acid and cetyltrimethylammonium bromide. Novel jack-shaped gold nanoparticles (102-105 nm) were obtained at a specific range of Ag(+) ion concentrations (62-102 µM). The crystalline structure of these nanoparticles was confirmed by high-resolution transmission electron microscopy. The influence of the perthiolated ß-cyclodextrin on the successful preparation of gold nanojacks was demonstrated. The jack-shaped gold nanoparticles showed strong absorption in the near infrared region and excellent catalytic activity for the electrochemical oxidation of H2O2.