Yanan Luo

Recent advances in electrochemical biosensors based on graphene two-dimensional nanomaterials.

Graphene as a star among two-dimensional nanomaterials has attracted tremendous research interest in the field of electrochemistry due to their intrinsic properties, including the electronic, optical, and mechanical properties associated with their planar structure. The marriage of graphene and electrochemical biosensors has created many ingenious biosensing strategies for applications in the areas of clinical diagnosis and food safety. This review provides a comprehensive overview of the recent advances in the development of graphene based electrochemical biosensors. Special attention is paid to graphene-based enzyme biosensors, immunosensors, and DNA biosensors. Future perspectives on high-performance graphene-based electrochemical biosensors are also discussed.

pH-Sensitive ZnO Quantum Dots–Doxorubicin Nanoparticles for Lung Cancer Targeted Drug Delivery

In this paper, we reported a ZnO quantum dots-based pH-responsive drug delivery platform for intracellular controlled release of drugs. Acid-decomposable, luminescent aminated ZnO quantum dots (QDs) were synthesized as nanocarriers with ultrasmall size (∼3 nm). The dicarboxyl-terminated poly(ethylene glycol) (PEG) had been introduced to NH2-ZnO QDs, which rendered it stable under physiological fluid. Moreover, a targeting ligand, hyaluronic acid (HA), was conjugated to ZnO QDs for specifically binding to the overexpressed glycoprotein CD44 by cancer cells. Doxorubicin (DOX) molecules were successfully loaded to PEG functionalized ZnO QDs via formation of metal-DOX complex and covalent interactions. The pH-sensitive ZnO QDs dissolved to Zn(2+) in acidic endosome/lysosome after uptake by cancer cells, which triggered dissociation of the metal-drug complex and a controlled DOX release. As result, a synergistic therapy was achieved due to incorporation of the antitumor effect of Zn(2+) and DOX.

Hyaluronic Acid-Modified Multifunctional Q-Graphene for Targeted Killing of Drug-Resistant Lung Cancer Cells.

Considering the urgent need to explore multifunctional drug delivery system for overcoming multidrug resistance, we prepared a new nanocarbon material Q-Graphene as a nanocarrier for killing drug-resistant lung cancer cells. Attributing to the introduction of hyaluronic acid and rhodamine B isothiocyanate (RBITC), the Q-Graphene-based drug delivery system was endowed with dual function of targeted drug delivery and fluorescence imaging. Additionally, doxorubicin (DOX) as a model drug was loaded on the surface of Q-Graphene via π-π stacking. Interestingly, the fluorescence of DOX was quenched by Q-Graphene due to its strong electron-accepting capability, and a significant recovery of fluorescence was observed, while DOX was released from Q-Graphene. Because of the RBITC labeling and the effect of fluorescence quenching/restoring of Q-Graphene, the uptake of nanoparticles and intracellular DOX release can be tracked. Overall, a highly promising multifunctional nanoplatform was developed for tracking and monitoring targeted drug delivery for efficiently killing drug-resistant cancer cells.

Hyaluronic acid-conjugated apoferritin nanocages for lung cancer targeted drug delivery

In this paper, we proposed a naturally derived protein cage based pH-responsive delivery system for intracellular prodrug controlled release. The drug delivery system is based on apoferritin as delivery vehicles to encapsulate the anticancer drug daunomycin (DN) and alleviate the side effect. The hydrophobic drug DN was encapsulated into the interior of apoferritin by the hydrophobic channels of the cage with swelling at slight acidic pH and electrostatic adsorption. The negatively charged poly-l-aspartic acid (PLAA) was further introduced into the apoferritin to absorb the positively charged DN. The mixture of PLAA and DN easily flew into the apoferritin cage and was stably stored in the physiological fluids. PLAA protected the leakage of DN and encapsulated a sufficient amount of drug molecules in the cage. To specifically target the tumor cells, the surface of apoferritin was modified with hyaluronic acid (HA) which can easily bind to the HA-receptor CD44. Here, human embryonic lung MRC-5 cells and lung cancer A549 cells were used to observe the specific binding of HA and morphological changes in vitro and examine the antitumor activity. This unique protein based drug delivery platform using the apoferritin cage shows great potential in the therapeutic administration of the anti-cancer agents.

A magnetic electrochemical immunosensor for the detection of phosphorylated p53 based on enzyme functionalized carbon nanospheres with signal amplification

Protein phosphorylation plays an important role in many biological processes and might be used as a potential biomarker in clinical diagnoses. We reported the development of a nanomaterial enhanced disposable immunosensor for ultrasensitive detection of phosphorylated p53 at Ser392 (phospho-p53392) using enzyme functionalization of carbon nanospheres (CNSs) as a signal amplification label and magnetic beads (MB) coupled with screen printed carbon electrodes as electrochemical transducers. In this work, horseradish peroxidase (HRP) and phospho-p53392 detection antibody (Ab2) were co-linked to CNSs (HRP–CNSs–Ab2) for signal amplification, and functionalized MB was used as a platform to capture a large amount of primary antibodies (Ab1). The proposed signal amplification strategy with a sandwich-type immunoreaction significantly enhanced the sensitivity of detection of biomarkers. Under optimal conditions, the immunosensor had a highly linear voltammetric response to the phospho-p53392 concentration in the range of 0.01 to 5 ng mL−1, with a detection limit of 3.3 pg mL−1. The results provided great potential for point-of-care detection of other phosphorylated proteins and clinical applications.

pH-Responsive ZnO Nanocluster for Lung Cancer Chemotherapy

Here, we demonstrated a pH-responsive nanocluster based on ZnO quantum dots (QDs) and investigated its potential in drug delivery with tumor-specific accumulation. The nanoclusters were composed of small single ZnO QDs by cross-linking dicarboxyl-terminated poly(ethylene glycol) (PEG), showing high stability and biocompatibility in physiological fluids. The clustered ZnO QDs were capable of loading a large quantity of doxorubicin (DOX) via complexation and covalent interactions. After cellular uptake, the drug was efficiently released because the carrier was completely dissolved; the metal-drug complex was disassembled in response to decreasing pH in the endosomes within tumor cells. Moreover, the viability of cancer cells was significantly decreased because the ZnO QDs exhibited cytotoxicity postdissolution and preferentially killed cancerous cells compared to normal cells. Furthermore, this pH-responsive PEG-cZnO QDs cluster system may be capable of tumor homing while circulating in the blood via the enhanced permeability and retention (EPR) effect.

Screening of antidote sensitivity using an acetylcholinesterase biosensor based on a graphene–Au nanocomposite

In this paper, we developed a new technique for in vitro screening of the therapeutic effects of three oxime compounds: obidoxime, 2-pralidoxime methiodide (2-PAM-I) and pyridine-2-aldoxime methochloride (2-PAM-Cl). Acetylcholinesterase (AChE) is first immobilized in a thin nanocomposite film composed of graphene and gold nanoparticles on a glassy carbon electrode by a self-assembly approach. The immobilized AChE in the nanocomposite is first exposed to an organophosphate agent, paraoxon-ethyl, and the enzyme activity is inhibited. The therapeutic effect is based on the reactivation capability of the oximes. AChE activity is measured by an electrochemical method. Our study indicated that oximes reactivation capacity is correlated to their molecular structures. Obidoxime, having dual oxime groups, showed higher reactivation capacity than 2-PAM compounds with a single oxime group. Due to the similar molecular structures of 2-PAM-I and 2-PAM-Cl, a slight difference between their reactivation capacities was found, and this difference is attributed to the stronger electron withdrawing ability of iodine ions than that of chloride ions. The proposed electrochemical method thus provides a new simple tool for new drug screening.

Graphene-like Metal-Free 2D Nanosheets for Cancer Imaging and Theranostics

The great success of graphene has driven the discovery and development of new 2D nanomaterials with different optical, electrical, and thermal properties. Compared with other graphene-like 2D nanomaterials, metal-free 2D nanomaterials hold great potential in biomedical applications since they exhibit much better biocompatibility and biosafety. We give an overview of some rapidly emerging graphene-like metal-free 2D nanomaterials including black phosphorus, hexagonal boron nitride, and graphitic carbon nitride, as well as 2D organic polymer-based nanomaterials, and highlight their impressive advances for bioimaging and cancer theranostics in recent years. The challenges and some thoughts on future perspectives in this field are also addressed.

SWCNTs@GQDs composites as nanocarriers for enzyme-free dual-signal amplification electrochemical immunoassay of cancer biomarker

Carcinoembryonic antigen (CEA) as a typical biomarker plays a remarkable role in various human physiological processes. A sensitive and rapid method should be developed to realize the precise diagnosis of cancer at its early stage. In this work, we successfully synthesized the peroxidase-like graphene quantum dots (GQDs) and utilized it to fabricate an enzyme-free electrochemical immunosensor towards CEA by forming a single-wall carbon nanotubes@GQDs (SWCNTs@GQDs) composite. In addition to the SWCNTs@GQDs, reduced graphene oxide-Au nanoparticles (rGO-Au NPs) with the huge specific surface area and excellent conductivity were employed to modify the electrodes, leading to a dual-signal amplification result. Both the electrochemical impedance spectroscopy and cyclic voltammetry measurements were performed to evaluate the interface properties of the layer-by-layer modified electrodes. The proposed electrochemical immunosensor displayed a good specificity and sensitivity towards the detection of CEA ranging from 50u202fpgu202fmL-1 to 650u202fpgu202fmL-1 with a low detection limit of 5.3u202fpgu202fmL-1. This simple and inexpensive immunosensor shows promising potential for the determination of other biomarkers in clinical translation.