Fuyao Liu

Conjugation of NaGdF4 upconverting nanoparticles on silica nanospheres as contrast agents for multi-modality imaging

Here, we report the covalently conjugation of lanthanide doped NaGdF4:Yb(3+), Er(3+)@NaGdF4 upconverting nanoparticles (UCNPs) on methylphosphonate functionalized silica nanospheres (pSi NPs) for in vivo upconversion luminescence (UCL), T1-weighted magnetic resonance (MR), and X-ray computed tomography (CT) multi-modality imaging. The nanocomposites (pSi@UCNPs) were synthesized by a facile ligand exchange strategy. The hydrophobic pSi@UCNPs were transferred into aqueous solution by surface coating Pluronic F127. The Pluronic F127 coated pSi@UCNPs (pSi@UCNPs@F127) exhibit excellent stability in biological medium, inappreciable cytotoxicity and negligible organ toxicity. The pSi@UCNPs@F127 also shows brighter UCL, and higher CT/MR enhancements than that of Pluronic F127 coated NaGdF4:Yb(3+), Er(3+)@NaGdF4 UCNP. In detail, the capability of pSi@UCNPs@F127 as high performance contrast agents for in vivo multi-modality (UCL/MR/CT) imaging is evaluated successfully through small-animal experiments.

Facile Preparation of Doxorubicin-Loaded Upconversion@Polydopamine Nanoplatforms for Simultaneous In Vivo Multimodality Imaging and Chemophotothermal Synergistic Therapy

The development of biosafe nanoplatforms with diagnostic and therapeutic multifunction is extremely demanded for designing cancer theranostic medicines. Here, a facile methodology is developed to construct a multifunctional nanotheranostic that gathers five functions, upconversion luminescence (UCL) imaging, T1-weighted magnetic resonance imaging (MRI), X-ray computed tomography (CT) imaging, photothermal therapy (PTT), and chemotherapy, into one single nanoprobe (named as UCNP@PDA5-PEG-DOX). For generating the UCNP@PDA5-PEG-DOX, a near-infrared light (NIR)-absorbing polydopamine (PDA) shell is directly coated on oleic-acid-capped β-NaGdF4:Yb(3+),Er(3+)@β-NaGdF4 upconverting nanoparticle (UCNP) core for the first time to form monodisperse, ultrastable, and noncytotoxic core-shell-structured nanosphere via water-in-oil microemulsion approach. When combined with 808 nm NIR laser irradiation, the UCNP@PDA5-PEG-DOX shows great synergistic interaction between PTT and the enhanced chemotherapy, resulting in completely eradicated mouse-bearing SW620 tumor without regrowth. In addition, leakage study, hemolysis assay, histology analysis, and blood biochemistry assay unambiguously reveal that the UCNP@PDA5-PEG has inappreciable cytotoxicity and negligible organ toxicity. The results provide explicit strategy for fabricating multifunctional nanoplatforms from the integration of UCNP with NIR-absorbing polymers, important for developing multi-mode nanoprobes for biomedical applications.

Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications

An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe3+, gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging.

Nanoparticle-based systems for T(1)-weighted magnetic resonance imaging contrast agents.

Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T1-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T1-weighted MRI/computed X-ray tomography (CT) and T1-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality.

Controllable synthesis of polydopamine nanoparticles in microemulsions with pH-activatable properties for cancer detection and treatment

Polydopamine nanoparticles (PDA NPs) which combine diagnostic and therapeutic functions are potentially useful in biomedicine. However, it is difficult to synthesize PDA NPs of a relatively small size (≤50 nm in diameter) using the traditional polymerization of dopamine monomers in an alkaline water-ethanol solution at room temperature. Herein, PDA NPs with average diameters ranging from 25 nm to 43 nm are prepared in a way which is similar to the silica-like reverse microemulsion process. The size of the PDA NPs can be modulated by changing the amount of dopamine monomers in the microemulsion. After conjugation with ferric ions (Fe3+), the poly(ethylene glycol) modified Fe-PDA NPs (termed as PEG-Fe-PDA NPs) exhibited pH-activatable magnetic resonance imaging (MRI) contrast and high photothermal performance. The combination of a small dimension and the pH-activatable MRI contrast can greatly facilitate tumor accumulation and increase the tumor imaging sensitivity against animal models in vivo. Completely inhibited tumor growth was achieved by the PEG-Fe-PDA NPs mediated by photothermal therapy with MRI guidance.

Thermal-mechanical fatigue behavior of a cast K417 nickel-based superalloy

The thermal-mechanical fatigue (TMF) behavior of cast K417 nickel-based superalloy was investigated under in-phase (IP) and out-of-phase (OP) loading in the temperature range from 400 to 850°C. The results revealed that the tendency to cyclic hardening under thermal-mechanical and isothermal fatigue was higher than that under static tensile testing at 850°C. Isothermal fatigue (IF) was observed to cause higher cyclic flow stress than TMF. At a corresponding strain amplitude, the thermal-mechanical fatigue life was lower than that of isothermal fatigue, and the TMF life of out-of-phase cycling was higher than that of in-phase cycling. Scanning electron microscopic observations of fracture surfaces and longitudinal sections revealed intergranular fracture under in-phase TMF which led to the decrease in fatigue life.

Lectin-conjugated Fe2O3@Au core@Shell nanoparticles as dual mode contrast agents for in vivo detection of tumor.

Here, we report the covalent conjugation of lectin on Fe2O3@Au core@shell nanoparticle (lectin-Fe2O3@Au NP) for T2-weighted magnetic resonance (MR) and X-ray computed tomography (CT) dual-modality imaging. The lectin-Fe2O3@Au NPs are prepared by coupling lectins to the Fe2O3@Au NP surfaces through bifunctional PEG NHS ester disulfide (NHS-PEG-S-S-PEG-NHS) linkers. After the nonspecific adsorption sites on the nanoparticle surface are blocked by thiolated PEG (PEG-SH), the lectin-Fe2O3@Au NPs exhibit excellent stability in biological medium and inappreciable cytotoxicity. A series of in vitro and in vivo experiments were then carried out for evaluating the capabilities of three selected lectin (ConA, RCA and WGA)-Fe2O3@Au NPs. The results revealed that the lectin-Fe2O3@Au NPs had a capacity not only for dual mode MR and CT imaging in vitro but also for MR and CT imaging of colorectal cancer in vivo. The experimental results also suggest that lectin could be used as tumor targeting ligand for synthesizing nanoparticle-based contrast agents.

Fabricating three-dimensional carbohydrate hydrogel microarray for lectin-mediated bacterium capturing.

Herein, a three-dimensional carbohydrate modified polyacrylamide hydrogel microarray (3D carbohydrate hydrogel microarray) has been fabricated and employed as micro-reactor for capturing Escherichia coli (E. coli) by multivalent binding of concanavalin A (Con A) with O-antigen on the cellular surface of E. coli and immobilized monosaccharides on hydrogel spot, and the interactions of type 1 fimbriae of E. coli with immobilized monosaccharides. Because of the transparent performance of polyacrylamide hydrogel, the captured E. coli can be directly observed by a conventional microscope under a bright-field mode. The experimental result demonstrates that α-D-mannopyranoside (Man-α) modified hydrogel surface shows high efficiency of E. coli capturing. The 3D Man-α hydrogel microarray-based assay shows reasonable low detection limit (1.0×10(4) cells/mL) and large dynamic range (1.0×10(5) to 1.0×10(9)cells/mL) for detecting E. coli. In addition, bacterial adhesion inhibition assay has been demonstrated by the interactions of E. coli with ten saccharides, and satisfactory results have been obtained.

A novel upconversion@polydopamine core@shell nanoparticle based aptameric biosensor for biosensing and imaging of cytochrome c inside living cells.

Herein, a novel upconversion@polydopamine core@shell nanoparticle (termed as UCNP@PDA NP) -based aptameric biosensor has been fabricated for the quantitative analysis of cytochrome c (Cyt c) inside living cells, which comprises an UCNP@PDA NP, acting as an internal reference and fluorescence quenching agent, and Cy3 modified aptamer enabling ratiometric quantitative Cyt c measurement. After the hybridization of Cy3 labeled aptamer with amino-terminated single DNA on the UCNP@PDA NP surface (termed as UCNP@PDA@AP), the fluorescence of Cy3 can be efficiently quenched by the PDA shell. With the spontaneous cellular uptake of UCNP@PDA@AP, the Cyt c aptamer dissociates from UCNP@PDA NP surface through formation of aptamer-Cyt c complex, resulting in concomitant activation of the Cy3 fluorescence. High amount of Cyt c leads to high fluorescence emission, enabling direct visualization/measurement of the Cyt c by fluorescence microscopy/spectroscopy. The steady upconversion luminescent (UCL) signals can be employed not only for intracellular imaging, but also as an internal reference for evaluating intracellular Cyt c amount using the ratio of fluorescence intensity of Cy3 with the UCL intensity of UCNP. The UCNP@PDA@AP shows a reasonable detection limit (20nM) and large dynamic range (50nM to 10μM, which covers the literature reported values (1-10μM) for cytosolic Cyt c in apoptotic cells) for detecting Cyt c in buffer with excellent selectivity. In addition, the UCNP@PDA@AP has been successfully used to monitor etoposide induced intracellular releasing of Cyt c, providing the possibility for cell-based screening of apoptosis-inducing drugs.

Thermo-mechanical fatigue of single crystal nickel-based superalloy DD8

The thermo-mechanical fatigue (TMF) behavior and the relevant microstructural evolution of the single crystal nickel-based superalloy DD8 were investigated. In-phase TMF lives were much shorter than those of out-of-phase TMF. The mechanism of TMF damage is discussed based on the microstructural evolution during TMF