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 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.

Amperometric aptasensor for carcinoembryonic antigen based on the use of bifunctionalized Janus nanoparticles as biorecognition-signaling element.

We report herein the design of a novel biosensing strategy for the detection of carcinoembryonic antigen (CEA), based on the use of Janus-type nanoparticles having Au and silica opposite faces as integrated electrochemical biorecognition-signaling system. The Janus nanoparticles were properly functionalized with horseradish peroxidase on the silica surface to act as signaling element, and a biotin thiol-modified anti-CEA DNA hairpin aptamer the Au face to assemble the biorecognition element. The sensing approach relies on the first specific recognition of CEA by the bifunctionalized Janus nanoparticles, causing unfolding of the DNA hairpin structure and unmasking the biotin residues at the aptamer chain. This CEA-Janus nanoparticle complex was then captured by avidin-modified Fe3O4@SiO2 NanoCaptors®, allowing further magnetic deposition on carbon screen printed electrodes for the amperometric detection of the cancer biomarker. The Janus nanoparticles-based aptasensor was able to detect CEA in the range from 1 to 5000 ng mL-1 (5.5 pM-28 nM) with a detection limit of 210 pg mL-1 (1.2 pM). The aptasensor also showed high reproducibility and storage stability, and was successfully validated in human serum.