Wenhao Dai

Fluorescent MoS2 Quantum Dots: Ultrasonic Preparation, Up-Conversion and Down-Conversion Bioimaging, and Photodynamic Therapy

Small size molybdenum disulfide (MoS2) quantum dots (QDs) with desired optical properties were controllably synthesized by using tetrabutylammonium-assisted ultrasonication of multilayered MoS2 powder via OH-mediated chain-like Mo-S bond cleavage mode. The tunable up-bottom approach of precise fabrication of MoS2 QDs finally enables detailed experimental investigations of their optical properties. The synthesized MoS2 QDs present good down-conversion photoluminescence behaviors and exhibit remarkable up-conversion photoluminescence for bioimaging. The mechanism of the emerging photoluminescence was investigated. Furthermore, superior (1)O2 production ability of MoS2 QDs to commercial photosensitizer PpIX was demonstrated, which has great potential application for photodynamic therapy. These early affording results of tunable synthesis of MoS2 QDs with desired photo properties can lead to application in fields of biomedical and optoelectronics.

Tunable Fabrication of Molybdenum Disulfide Quantum Dots for Intracellular MicroRNA Detection and Multiphoton Bioimaging

Molybdenum disulfide (MoS2 ) quantum dots (QDs) (size <10 nm) possess attractive new properties due to the quantum confinement and edge effects as graphene QDs. However, the synthesis and application of MoS2 QDs has not been investigated in great detail. Here, a facile and efficient approach for synthesis of controllable-size MoS2 QDs with excellent photoluminescence (PL) by using a sulfuric acid-assisted ultrasonic route is developed for this investigation. Various MoS2 structures including monolayer MoS2 flake, nanoporous MoS2 , and MoS2 QDs can be yielded by simply controlling the ultrasonic durations. Comprehensive microscopic and spectroscopic tools demonstrate that the MoS2 QDs have uniform lateral size and possess excellent excitation-independent blue PL. The as-generated MoS2 QDs show high quantum yield of 9.65%, long fluorescence lifetime of 4.66 ns, and good fluorescent stability over broad pH values from 4 to 10. Given the good intrinsic optical properties and large surface area combined with excellent physiological stability and biocompatibility, a MoS2 QDs-based intracellular microRNA imaging analysis system is successfully constructed. Importantly, the MoS2 QDs show good performance as multiphoton bioimaging labeling. The proposed synthesis strategy paves a new way for facile and efficient preparing MoS2 QDs with tunable-size for biomedical imaging and optoelectronic devices application.

Three-dimensional Nitrogen-Doped Graphene Supported Molybdenum Disulfide Nanoparticles as an Advanced Catalyst for Hydrogen Evolution Reaction

An efficient three-dimensional (3D) hybrid material of nitrogen-doped graphene sheets (N-RGO) supporting molybdenum disulfide (MoS2) nanoparticles with high-performance electrocatalytic activity for hydrogen evolution reaction (HER) is fabricated by using a facile hydrothermal route. Comprehensive microscopic and spectroscopic characterizations confirm the resulting hybrid material possesses a 3D crumpled few-layered graphene network structure decorated with MoS2 nanoparticles. Electrochemical characterization analysis reveals that the resulting hybrid material exhibits efficient electrocatalytic activity toward HER under acidic conditions with a low onset potential of 112 mV and a small Tafel slope of 44 mV per decade. The enhanced mechanism of electrocatalytic activity has been investigated in detail by controlling the elemental composition, electrical conductance and surface morphology of the 3D hybrid as well as Density Functional Theory (DFT) calculations. This demonstrates that the abundance of exposed active sulfur edge sites in the MoS2 and nitrogen active functional moieties in N-RGO are synergistically responsible for the catalytic activity, whilst the distinguished and coherent interface in MoS2/N-RGO facilitates the electron transfer during electrocatalysis. Our study gives insights into the physical/chemical mechanism of enhanced HER performance in MoS2/N-RGO hybrids and illustrates how to design and construct a 3D hybrid to maximize the catalytic efficiency.

Highly Sensitive and Selective MicroRNA Detection Based on DNA-Bio-Bar-Code and Enzyme-Assisted Strand Cycle Exponential Signal Amplification

Herein, a highly sensitive and selective microRNA (miRNA) detection strategy using DNA-bio-bar-code amplification (BCA) and Nb·BbvCI nicking enzyme-assisted strand cycle for exponential signal amplification was designed. The DNA-BCA system contains a locked nucleic acid (LNA) modified DNA probe for improving hybridization efficiency, while a signal reported molecular beacon (MB) with an endonuclease recognition site was designed for strand cycle amplification. In the presence of target miRNA, the oligonucleotides functionalized magnetic nanoprobe (MNP-DNA) and gold nanoprobe (AuNP-DNA) with numerous reported probes (RP) can hybridize with target miRNA, respectively, to form a sandwich structure. After sandwich structures were separated from the solution by the magnetic field, the RP were released under high temperature to recognize the MB and cleaved the hairpin DNA to induce the dissociation of RP. The dissociated RP then triggered the next strand cycle to produce exponential fluorescent signal amplification for miRNA detection. Under optimized conditions, the exponential signal amplification system shows a good linear range of 6 orders of magnitude (from 0.3 pM to 3 aM) with limit of detection (LOD) down to 52.5 zM, while the sandwich structure renders the system with high selectivity. Meanwhile, the feasibility of the proposed strategy for cell miRNA detection was confirmed by analyzing miRNA-21 in HeLa lysates. Given the high-performance for miRNA analysis, the strategy has a promising application in biological detection and in clinical diagnosis.

Multifunctional Poly(l-lactide)–Polyethylene Glycol-Grafted Graphene Quantum Dots for Intracellular MicroRNA Imaging and Combined Specific-Gene-Targeting Agents Delivery for Improved Therapeutics

Photoluminescent (PL) graphene quantum dots (GQDs) with large surface area and superior mechanical flexibility exhibit fascinating optical and electronic properties and possess great promising applications in biomedical engineering. Here, a multifunctional nanocomposite of poly(l-lactide) (PLA) and polyethylene glycol (PEG)-grafted GQDs (f-GQDs) was proposed for simultaneous intracellular microRNAs (miRNAs) imaging analysis and combined gene delivery for enhanced therapeutic efficiency. The functionalization of GQDs with PEG and PLA imparts the nanocomposite with super physiological stability and stable photoluminescence over a broad pH range, which is vital for cell imaging. Cell experiments demonstrate the f-GQDs excellent biocompatibility, lower cytotoxicity, and protective properties. Using the HeLa cell as a model, we found the f-GQDs effectively delivered a miRNA probe for intracellular miRNA imaging analysis and regulation. Notably, the large surface of GQDs was capable of simultaneous adsorption of agents targeting miRNA-21 and survivin, respectively. The combined conjugation of miRNA-21-targeting and survivin-targeting agents induced better inhibition of cancer cell growth and more apoptosis of cancer cells, compared with conjugation of agents targeting miRNA-21 or survivin alone. These findings highlight the promise of the highly versatile multifunctional nanocomposite in biomedical application of intracellular molecules analysis and clinical gene therapeutics.

Aptamer-Conjugated Graphene Quantum Dots/Porphyrin Derivative Theranostic Agent for Intracellular Cancer-Related MicroRNA Detection and Fluorescence-Guided Photothermal/Photodynamic Synergetic Therapy

Multifunctional theranostic platform coupling diagnostic and therapeutic functions holds great promise for personalized nanomedicine. Nevertheless, integrating consistently high performance in one single agent is still challenging. This work synthesized a sort of porphyrin derivatives (P) with high singlet oxygen generation ability and graphene quantum dots (GQDs) possessing good fluorescence properties. The P was conjugated to polyethylene glycol (PEG)ylated and aptamer-functionalized GQDs to gain a multifunctional theranostic agent (GQD-PEG-P). The resulting GQD-PEG-P displayed good physiological stability, excellent biocompatibility and low cytotoxicity. The intrinsic fluorescence of the GQDs could be used to discriminate cancer cells from somatic cells, whereas the large surface facilitated gene delivery for intracellular cancer-related microRNA (miRNA) detection. Importantly, it displayed a photothermal conversion efficiency of 28.58% and a high quantum yield of singlet oxygen generation up to 1.08, which enabled it to accomplish advanced photothermal therapy (PTT) and efficient photodynamic therapy (PDT) for cancer treatment. The combined PTT/PDT synergic therapy led to an outstanding therapeutic efficiency for cancer cell treatment.

One-Step Hydrothermal Fabrication of Three-dimensional MoS 2 Nanoflower using Polypyrrole as Template for Efficient Hydrogen Evolution Reaction

Herein, a facile and cost-effective strategy for hydrothermal synthesis of three-dimensional (3D) MoS2 with adequate active edge sites and advanced hydrogen evolution reaction (HER) performance using polypyrrole (PPy) as template is reported. The MoS2 is first thermally nucleated using hexaammonium heptamolybdate tetrahydrate (NH4)6Mo7O24·4H2O and thiourea as precursor in the presence of PPy, and then they are further annealed to remove PPy at higher temperature to generate 3D MoS2-P. Morphology and composition characterizations reveal that the 3D MoS2-P exhibits a nanoflower morphology. It presents larger stretched “thin folding leaves” and higher mesoporous volume of 0.608 cm3 g−1 than the MoS2 without PPy as template. Importantly, the 3D MoS2-P shows enhanced HER catalytic activity (onset potential at −100 mV) than previously reports that MoS2-based HER catalysts. The large “thin folding leaves” possessing efficient edge active sites and defects are responsible to for the enhanced HER performance, while the high mesoporous volume facilitates the transfer of reaction substrate. Our study provides a facile and cost-effective method for synthesis of 3D MoS2 with advanced HER performances, which has great potential for larger-scale production and practical industrial applications.

Fabricating Pt/Sn–In2O3 Nanoflower with Advanced Oxygen Reduction Reaction Performance for High-Sensitivity MicroRNA Electrochemical Detection

Herein, an efficient electrochemical tracer with advanced oxygen reduction reaction (ORR) performance was designed by controllably decorating platinum (Pt) (diameter, 1 nm) on the surface of compositionally tunable tin-doped indium oxide nanoparticle (Sn-In2O3) (diameter, 25 nm), and using the Pt/Sn-In2O3 as electrochemical tracer and interfacial term hairpin capture probe, a facile and ultrasensitive microRNA (miRNA) detection strategy was developed. The morphology and composition of the generated Pt/Sn-In2O3 NPs were comprehensively characterized by spectroscopic and microscopic measurements, indicating numerous Pt uniformly anchored on the surface of Sn-In2O3. The interaction between Pt and surface Sn as well as high Pt(111) exposure resulted in the excellent electrochemical catalytic ability and stability of the Pt/Sn-In2O3 ORR. As proof-of-principle, using streptavidin (SA) functionalized Pt/Sn-In2O3 (SA/Pt/Sn-In2O3) as electrochemical tracer to amplify the detectable signal and a interfacial term hairpin probe for target capture probe, a miRNA biosensor with a linear range from 5 pM to 0.5 fM and limit of detection (LOD) down to 1.92 fM was developed. Meanwhile, the inherent selectivity of the term hairpin capture probe endowed the biosensor with good base discrimination ability. The good feasibility for real sample detection was also demonstrated. The work paves a new avenue to fabricate and design high-effective electrocatalytic tracer, which have great promise in new bioanalytical applications.

Peroxidase-like Fe3O4 nanocomposite for activatable reactive oxygen species generation and cancer theranostics

Photodynamic therapy (PDT) that utilizes apoptosis induced by reactive oxygen species (ROS) has received extensive attention in practical cancer therapy. However, the hypoxic microenvironment of solid tumors significantly limits the efficacy of therapy. Approaches that overcome the barriers to PDT in hypoxic conditions by simultaneously producing ROS exogenously and improving the oxygenation of tumors have never been studied. Herein, an activatable ROS platform was designed that uses the high reactivity of peroxidase-like Fe3O4 toward endogenous hydrogen peroxide (H2O2) to concurrently generate ˙OH as a therapeutic agent and provide O2 for oxygen-dependent PDT. Multifunctional chitosan-encapsulated Fe3O4 nanoparticles modified with CuS and porphyrin (FCCP NPs) were fabricated to achieve multimodal imaging and synergetic therapy. The FCCP NPs possess enhanced intrinsic peroxidase mimetic activity to produce ROS and O2 from endogenous H2O2. Multimodal imaging in vivo, including photoacoustic imaging (PAI), magnetic resonance imaging (MRI), photoluminescence imaging (PLI), and photothermal imaging (PTI), exploits the tumor-targeting property of FCCP NPs upon intravenous injection. It can induce cancer cell death with remarkable efficiency both in vitro and in vivo via synergetic treatment with PDT and photothermal therapy (PTT). This study demonstrates the promise of the activatable generation of ROS and O2 for PDT with nanotechnology to overcome a current deficiency in cancer therapies.

Erythrocyte–Cancer Hybrid Membrane Camouflaged Hollow Copper Sulfide Nanoparticles for Prolonged Circulation Life and Homotypic-Targeting Photothermal/Chemotherapy of Melanoma

Cellular-membrane-coated nanoparticles have increasingly been pursued to leverage the natural cell functions for enhancing biocompatibility and improved therapeutic efficacy. Taking advantage of specialized cell membranes or combining functions from different membrane types facilitates the strengthening of their functionality. Herein, we fuse membrane materials derived from red blood cells (RBCs) and melanoma cells (B16-F10 cells) to create a hybrid biomimetic coating (RBC-B16), and RBC-B16 hybrid membrane camouflaged doxorubicin (DOX)-loaded hollow copper sulfide nanoparticles (DCuS@[RBC-B16] NPs) are fabricated for combination therapy of melanoma. The DCuS@[RBC-B16] NPs are comprehensively characterized, showing the inherent properties of the both source cells. Compared to the bare CuS NPs, the DCuS@[RBC-B16] NPs exhibit highly specific self-recognition to the source cell line in vitro and achieve markedly prolonged circulation lifetime and enhanced homogeneous targeting abilities in vivo inherited from the source cells. Thus, the DOX-loaded [RBC-B16]-coated CuS NP platform exhibits excellent synergistic photothermal/chemotherapy with about 100% melanoma tumor growth inhibition rate. The reported strategy may contribute to personalized nanomedicine of various tumors by combining the RBCs with a homotypic cancer membrane accordingly on the surface of the nanoparticle.