Jinsong Ren

Graphene Oxide: Intrinsic Peroxidase Catalytic Activity and Its Application to Glucose Detection

Carboxyl-modified graphene oxide (GO-COOH) possesses intrinsic peroxidase-like activity that can catalyze the reaction of peroxidase substrate 3,3,5,5-tetramethyl-benzidine (TMB) in the presence of H2O2 to produce a blue color reaction. A simple, cheap, and highly sensitive and selective colorimetric method for glucose detection has been developed and will facilitate the utilization of GO-COOH intrinsic peroxidase activity in medical diagnostics and biotechnology.

Catalytically Active Nanomaterials: A Promising Candidate for Artificial Enzymes

Natural enzymes, exquisite biocatalysts mediating every biological process in living organisms, are able to accelerate the rate of chemical reactions up to 10(19) times for specific substrates and reactions. However, the practical application of enzymes is often hampered by their intrinsic drawbacks, such as low operational stability, sensitivity of catalytic activity to environmental conditions, and high costs in preparation and purification. Therefore, the discovery and development of artificial enzymes is highly desired. Recently, the merging of nanotechnology with biology has ignited extensive research efforts for designing functional nanomaterials that exhibit various properties intrinsic to enzymes. As a promising candidate for artificial enzymes, catalytically active nanomaterials (nanozymes) show several advantages over natural enzymes, such as controlled synthesis in low cost, tunability in catalytic activities, as well as high stability against stringent conditions. In this Account, we focus on our recent progress in exploring and constructing such nanoparticulate artificial enzymes, including graphene oxide, graphene-hemin nanocomposites, carbon nanotubes, carbon nanodots, mesoporous silica-encapsulated gold nanoparticles, gold nanoclusters, and nanoceria. According to their structural characteristics, these enzyme mimics are categorized into three classes: carbon-, metal-, and metal-oxide-based nanomaterials. We aim to highlight the important role of catalytic nanomaterials in the fields of biomimetics. First, we provide a practical introduction to the identification of these nanozymes, the source of the enzyme-like activities, and the enhancement of activities via rational design and engineering. Then we briefly describe new or enhanced applications of certain nanozymes in biomedical diagnosis, environmental monitoring, and therapeutics. For instance, we have successfully used these biomimetic catalysts as colorimetric probes for the detection of cancer cells, nucleic acids, proteins, metal ions, and other small molecules. In addition, we also introduce three exciting advances in the use of efficient modulators on artificial enzyme systems to improve the catalytic performance of existing nanozymes. For example, we report that graphene oxide could serve as a modulator to greatly improve the catalytic activity of lysozyme-stabilized gold nanoclusters at neutral pH, which will have great potential for applications in biological systems. We show that, through the incorporation of modulator into artificial enzymes, we can offer a facile but highly effective way to improve their overall catalytic performance or realize the catalytic reactions that were not possible in the past. We expect that nanozymes with unique properties and functions will attract increasing research interest and lead to new opportunities in various fields of research.

Microwave assisted one-step green synthesis of cell-permeable multicolor photoluminescent carbon dots without surface passivation reagents

A facile, economic and green one-step microwave synthesis route towards photoluminescent carbon dots is proposed. The preparation requires a carbohydrate (glycerol, glycol, glucose, sucrose, etc.) and a tiny amount of an inorganic ion, and can finish in just a few minutes, no surface passivation reagent is needed. The carbon dots are biologically compatible and show favorable optical properties and have potential applications in biolabeling and bioimaging.

Label-free colorimetric detection of single nucleotide polymorphism by using single-walled carbon nanotube intrinsic peroxidase-like activity.

Single-walled carbon nanotubes (SWNTs) have been considered to be leading candidates for nanodevice applications and novel drug delivery. Intriguingly, recent studies have shown that SWNTs have catalytic activity even in the absence of catalytic factors. Since hydrogen peroxide is an important oxidizing agent in biological systems, the catalytic reaction of SWNTs with H2O2 has received much attention. The SWNT catalytic mechanism is much debated, but it has been suggested that it is related to trace amounts of metal catalyst in SWNTs. H2O2 is a major reactive oxygen species in living organisms, and its overproduction is implicated in the development of numerous inflammatory diseases, such as atherosclerosis, chronic obstructive pulmonary disease, and hepatitis. Furthermore, as a product of many enzyme-catalyzed reactions, H2O2 can act as an indicator to monitor the quantity of biologically important molecules, such as glucose. Therefore, studying the catalytic reaction of SWNTs with H2O2 might offer a promising application for disease diagnosis and for the design of SWNT-based sensors. In this work, we report that SWNTs possess intrinsic peroxidase-like activity. That the catalytic activity does not depend on trace amounts of metal catalyst in the SWNTs is evidenced by energy-dispersive X-ray (EDX) analysis. In the presence of H2O2, SWNTs catalyze the reaction of the peroxidase substrate 3,3,5,5-tetramethylbenzidine (TMB) thereby producing a color change (Scheme 1). Our results indicate that the catalytic efficiency of SWNTs is strongly dependent on pH, temperature, and H2O2 concentration, similar to horseradish peroxidase (HRP). More importantly, we compared the catalytic efficiency of SWNTs containing different amounts of cobalt residues. The results clearly show that the observed “catalytic” effect of SWNTs can be attributed to their intrinsic properties rather than metal residues. Peroxidase activity has a great potential for practical application and has been used in the bioremediation of waste water or as diagnostic kits. As peroxidase mimics, SWNTs were used here for label-free colorimetric detection of disease-associated single-nucleotide polymorphism (SNP) with a direct detection limit of 1 nm based on the color reaction of TMB. It is well known that SNP detection is very important, and different kinds of detection methods have been reported; however, to our knowledge, this is the first demonstration of applying intrinsic SWNT peroxidase-like activity and color change for this purpose. This work will provide new insights into the utilization of SWNT peroxidase-like activity. To increase SWNT solubility in aqueous solution, we treated SWNTs with a mixture of concentrated sulfuric and nitric acids, as described previously. Figure S1 in the Supporting Information shows the mixed solution of H2O2 and TMB in the presence or absence of SWNTs. In the absence of SWNTs, the color of the solution does not change in 12 h; however, in the presence of SWNTs, the color changes from black to blue immediately. This result suggests that SWNTs can catalyze the reaction of TMB in the presence of [a] Y. Song, X. Wang, C. Zhao, K. Qu, Dr. J. Ren, Prof. X. Qu Laboratory of Chemical Biology Division of Biological Inorganic Chemistry State Key Laboratory of Rare Earth Resource Utilization Graduate School of the Chinese Academy of Sciences Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun, Jilin 130022 (China) Fax: (+86)431-85262656 E-mail : xqu@ciac.jl.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.20090902643. Scheme 1. Schematic illustration of SWNTs catalyzing the reaction of peroxidase substrate TMB in the presence of H2O2 to give the blue product oxidized TMB (oxTMB).

A graphene functionalized electrochemical aptasensor for selective label-free detection of cancer cells

Here we report an electrochemical sensor that can realize label-free cancer cell detection using the first clinical trial II used aptamer AS1411 and functionalized graphene. By taking advantages of AS1411 high binding affinity and specificity to the overexpressed nucleolin on the cancer cell surface, our developed electrochemical aptasensor can distinguish cancer cells and normal ones and detect as low as one thousand cells. With DNA hybridization technique, this E-DNA sensor can be regenerated and reusable for cancer cell detection. Our work gives a good example for label-free cancer cell detection based on aptamer and graphene-modified electrode.

Near‐Infrared Light‐Triggered, Targeted Drug Delivery to Cancer Cells by Aptamer Gated Nanovehicles

A novel cell-targeting, near-infrared light-responsive drug delivery platform based on mesoporous silica-coated gold nanorods that are surface-functionalized with aptamer DNA is constructed. Aptamer DNA is used as both capping and targeting agent. In vitro studies show the feasibility of using this nanocarrier for targeted and noninvasive remote controlled drug delivery and photothermal therapy.

Using Graphene Oxide High Near-Infrared Absorbance for Photothermal Treatment of Alzheimer's Disease

A novel strategy to dissociate amyloid aggregation is presented, using localised heat generation from a clinically used amyloid staining dye, thioflavin-S (ThS)-modified graphene oxide (GO) under NIR laser irradiation. Compared to traditional chemotherapies, photothermal therapy shows reduced side effects and improved selectivity and safety.

Polyvalent Nucleic Acid/Mesoporous Silica Nanoparticle Conjugates: Dual Stimuli‐Responsive Vehicles for Intracellular Drug Delivery

The distinctive characteristics of mesoporous silica nanoparticles (MSPs) such as thermal stability, tunable pore sizes, large load capacity, and the ease of surface functionalization make these scaffolds ideal for the design of nanodevices and “on-command” delivery applications. To date, several MSPbased controlled-release systems have been synthesized by using different kinds of capping agents including organic molecules, nanoparticles, and supramolecular assemblies. “On-demand” release systems that respond to a range of stimuli, including redox, 4a,5] pH or temperature, enzymes, competitive binding, and photoirradiation 4b,9] have recently been reported. Despite these burgeoning achievements, many of the existing capping systems have disadvantages such as the use of stimuli that are complicated and/or difficult to apply, poor applicability in aqueous solutions and biocompatibility, and the toxicity of the capping agents used. In particular, regardless of recent reports on capped MSPs that can be uncapped by certain enzymes or carbohydrates, the utility of MSP-based devices involving biomolecules for real delivery systems is still in its infancy. Therefore, the search for effective systems that, in particular, respond to internal biological stimuli still remains a big challenge in this field. Herein we describe the design and construction of a stimuli-responsive vehicle for intracellular drug delivery using a polyvalent nucleic acid/MSP “click” conjugate that responds to both external and endogenous activation. Nucleic acids have been recognized as attractive building blocks for nanotechnology and materials science owing to the remarkable specificity and versatility of these units. The unique structural motif and self-recognition properties of duplex DNA, including temperature-dependent assembly, as well as the enzymatic recognition of specific encoded bases, may be applied as triggers for functional DNA manipulation. As shown in Figure 1, self-complementary duplex DNA was anchored to the openings of the MSPs and was utilized as a cap for trapping the guest molecules within the porous

Incorporating Graphene Oxide and Gold Nanoclusters: A Synergistic Catalyst with Surprisingly High Peroxidase-Like Activity Over a Broad pH Range and its Application for Cancer Cell Detection

A synergistic graphene oxide-gold nanocluster (GO-AuNC) hybrid has been constructed as an enzyme mimic that is able to show high catalytic activity over a broad pH range, especially at neutral pH. Importantly, the target-functionalized hybrid has been applied as a robust nanoprobe for selective, quantitative, and fast colorimetric detection of cancer cells.

Hydrophobic Anticancer Drug Delivery by a 980 nm Laser-Driven Photothermal Vehicle for Efficient Synergistic Therapy of Cancer Cells In Vivo

A novel 980 nm laser-driven hydrophobic anticancer drug-delivery platform based on hollow CuS nanoparticles is constructed in this work. The excellent synergistic therapy combining drug treatment and photothermal ablation of cancer cells both in vitro and in vivo is demonstrated, which opens up new opportunities for biological and medical applications.