Jichao Zhang

Multifunctional photosensitizer-conjugated core–shell Fe3O4@NaYF4:Yb/Er nanocomplexes and their applications in T2-weighted magnetic resonance/upconversion luminescence imaging and photodynamic therapy of cancer cells

Due to non-invasive deep imaging and therapy, multifunctional agents of magnetic resonance (MR)/upconversion luminescence (UCL) imaging and photodynamic therapy (PDT) play an important role in clinical diagnosis and treatment of cancers, and also in the assessment of therapy effect. In this paper, tetra-sulfonic phthalocyanine aluminium (AlPcS4) photosensitizers-conjugated Fe3O4@NaYF4:Yb/Er (NPs-AlPcS4) nanocomplexes were synthesized for the T2-weighted MR/UCL imaging and PDT of cancer cells. The PEG-coated Fe3O4@NaYF4:Yb/Er nanoparticles (NPs) with a core–shell structure showed strong T2-weighted MR relaxivity (r2 = 42.131 mM−1 s−1) and UCL emission in the visible region (the bands at about 654–674 nm, 545 nm and 524 nm), and were conjugated successfully with AlPcS4 photosensitizer by electrostatic interaction. By direct observation of XFM and staining with Prussian blue, the element distribution and location of NPs in MCF-7 cells were characterized, respectively. Under irradiation from a 980 nm laser, the death ratio of MCF-7 cells incubated with NPs-AlPcS4 nanocomplexes could be up to about 70%. The results indicated that the as-prepared NPs-AlPcS4 nanocomplexes would be a potential candidate as multifunctional nanoprobes for the dual-modal T2-weighted MR/UCL imaging and PDT of cancers in the future.

Microfabricated on-chip integrated Au–Ag–Au three-electrode system for in situ mercury ion determination

In this paper, a new two-step photolithography fabrication method is used for the fabrication of an on-chip integrated two-metal electrode system, with a Ag reference electrode and two gold electrodes used as working and counter electrodes, respectively. Combined with a microfluidic channel, the total detector has the advantages of ease of use, low analyte consumption, fast sensing time and is suited for in situ target metal ion determination. Herein, the three-electrode system was used for Hg(2+) ion measurement, and both the capabilities of Au working and Ag reference electrodes were characterized by using electrochemical techniques. The results show that the as-prepared on-chip integrated electrochemical detector performed with high sensitivity and good reproducibility in Hg(2+) determination. The detection range extends from 10 to 1000 ppb with a good linear correlation, and the detection limit is low to 3 ppb (S/N = 3). Our method provides a rapid and effective, miniaturized electrochemical analysis platform in Hg(2+) measurement and demonstrates great potential for the application of in situ or on-line mercuric pollutant analysis.

Fates of Fe3O4 and Fe3O4@SiO2 nanoparticles in human mesenchymal stem cells assessed by synchrotron radiation-based techniques

Superparamagnetic iron oxide nanoparticles (SPIOs) have been widely used as the magnetic resonance imaging (MRI) contrast agent in biomedical studies and clinical applications, with special interest recently in in vivo stem cell tracking. However, a full understanding of the fate of SPIOs in cells has not been achieved yet, which is particularly important for stem cells since any change of the microenvironment may disturb their propagation and differentiation behaviors. Herein, synchrotron radiation-based X-ray fluorescence (XRF) in combination with X-ray absorption spectroscopy (XAS) were used to in situ reveal the fate of Fe3O4 and Fe3O4@SiO2 NPs in human mesenchymal stem cells (hMSCs), in which the dynamic changes of their distribution and chemical speciation were precisely determined. The XAS analysis evidences that Fe3O4 NPs cultured with hMSCs are quite stable and almost keep their initial chemical form up to 14 days, which is contradictory to the previous report that Fe3O4 NPs were unstable in cell labeling assessed by using a simplified lysosomal model system. Coating with a SiO2 shell, Fe3O4@SiO2 NPs present higher stability in hMSCs without detectable changes of their chemical form. In addition, XRF analysis demonstrates that Fe3O4@SiO2 NPs can label hMSCs in a high efficiency manner and are solely distributed in cytoplasm during cell proliferation, making it an ideal probe for in vivo stem cell tracking. These findings with the help of synchrotron radiation-based XAS and XRF improve our understanding of the fate of SPIOs administered to hMSCs and will help the future design of SPIOs for safe and efficient stem cells tracking.

Nanodiamonds act as Trojan horse for intracellular delivery of metal ions to trigger cytotoxicity.

BackgroundNanomaterials hold great promise for applications in the delivery of various molecules with poor cell penetration, yet its potential for delivery of metal ions is rarely considered. Particularly, there is limited insight about the cytotoxicity triggered by nanoparticle-ion interactions. Oxidative stress is one of the major toxicological mechanisms for nanomaterials, and we propose that it may also contribute to nanoparticle-ion complexes induced cytotoxicity.MethodsTo explore the potential of nanodiamonds (NDs) as vehicles for metal ion delivery, we used a broad range of experimental techniques that aimed at getting a comprehensive assessment of cell responses after exposure of NDs, metal ions, or ND-ion mixture: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Trypan blue exclusion text, optical microscope observation, synchrotron-based scanning transmission X-ray microscopy (STXM) and micro X-ray fluorescence (μXRF) microscopy, inductively coupled plasma-mass spectrometry (ICP-MS), reactive oxygen species (ROS) assay and transmission electron microscopy (TEM) observation. In addition, theoretical calculation and molecular dynamics (MD) computation were used to illustrate the adsorption properties of different metal ion on NDs as well as release profile of ion from ND-ion complexes at different pH values.ResultsThe adsorption capacity of NDs for different metal ions was different, and the adsorption for Cu2+ was the most strong among divalent metal ions. These different ND-ion complexes then had different cytotoxicity by influencing the subsequent cellular responses. Detailed investigation of ND-Cu2+ interaction showed that the amount of released Cu2+ from ND-Cu2+ complexes at acidic lysosomal conditions was much higher than that at neutral conditions, leading to the elevation of intracellular ROS level, which triggered cytotoxicity. By theoretical approaches, we demonstrated that the functional carbon surface and cluster structures of NDs made them good vehicles for metal ions delivery.ConclusionsNDs played the Trojan horse role by allowing large amounts of metal ions accumulate into living cells followed by subsequent release of ions in the interior of cells, which then led to cytotoxicity. The present experimental and theoretical results provide useful insight into understanding of cytotoxicity triggered by nanoparticle-ion interactions, and open new ways in the interpretation of nanotoxicity.

A facile fabrication route for binary transition metal oxide-based Janus nanoparticles for cancer theranostic applications

Janus nanoparticles (JNPs) have multiple configurations for molecular imaging, targeting, and therapeutic effects on cancers; these properties have made these particles attractive for biomedical applications. Nonetheless, smart strategies for the controlled synthesis in a liquid phase and exploration of the appropriate applications of JNPs remain a challenge. In this study, a unique liquid-phase method was applied to fabricate Mn3O4-TiO2/ZnO/Fe3O4 multifunctional binary transition metal oxide-based JNPs, using the concept of epitaxial growth and lattice mismatch among synthesized materials. Transmission electron microscopy and scanning transmission electron microscopy results revealed that the created materials are embedded in the form of dimers with good dispersion and homogeneous growth in a nonpolar solvent. Pluronic® F-127-coated Mn3O4- TiO2 JNPs were utilized as a contrast agent in T1-weighted magnetic resonance imaging (MRI) and in photodynamic therapy (PDT) for cancers in vitro and in vivo. In vivoT1-weighted MRI of the heart, liver, and kidneys in mice after intravenous injection of the nanoparticles revealed high sensitivity and biocompatibility of as-synthesized Mn3O4-TiO2 JNPs. Results of synchrotron X-ray fluorescence microscopy mapping showed the stability of the nanocomposites and efficiency of penetration into the cytoplasm and perinuclear area. Inorganic TiO2 photosensitizers showed promising tumor ablation performance in PDT in vitro and in vitro at low intensity of UV irradiation (5.6 mW.cm–2) because of their ultrasmall size and photodegradable stability. These results reveal that multifunctional Mn3O4-TiO2 JNPs enhance a T1-weighted MRI contrast and have excellent properties for PDT and therefore, may be a novel agent for cancer theranostics.

Transportation and fate of gold nanoparticles in oilseed rape

Gold nanoparticles (AuNPs) are often used as nanoscale vehicles to deliver drugs or biomolecules due to low cytotoxicity and high biocompatibility. Current research focuses on their application in cell or animal models, while their use in plants is limited because their ecotoxicological impact is poorly documented. Here, we examine the toxicity and fate of AuNPs in plants using oilseed rape as a model. We show that AuNPs will not affect the germination of rape seeds as well as the growth of the plantlet. Significantly, we demonstrate the effective translocation of AuNPs in plant tissues, and AuNPs will not interfere with the natural distribution of mineral nutrient elements in plant tissues. Our results demonstrate the mild effect of AuNPs on the growth of oilseed rape seedlings and suggest their potential application as vehicles for gene delivery in plants.

Hydrogen Sulfide-Activatable Second Near-Infrared Fluorescent Nanoassemblies for Targeted Photothermal Cancer Therapy

Near-infrared (NIR)-II fluorescence agents hold great promise for deep-tissue photothermal therapy (PTT) of cancers, which nevertheless remains restricted by the inherent nonspecificity and toxicity of PTT. In response to this challenge, we herein develop a hydrogen sulfide (H2S)-activatable nanostructured photothermal agent (Nano-PT) for site-specific NIR-II fluorescence-guided PTT of colorectal cancer (CRC). Our in vivo studies reveal that this theranostic Nano-PT probe is specifically activated in H2S-rich CRC tissues, whereas it is nonfunctional in normal tissues. Activation of Nano-PT not only emits NIR-II fluorescence with deeper tissue penetration ability than conventional fluorescent probes but also generates high NIR absorption resulting in efficient photothermal conversion under NIR laser irradiation. Importantly, we establish NIR-II imaging-guided PTT of CRC by applying the Nano-PT agent in tumor-bearing mice, which results in complete tumor regression with minimal nonspecific damages. Our studies thus shed light on the development of cancer biomarker-activated PTT for precision medicine.

Synchrotron-based X-ray microscopy for sub-100 nm resolution cell imaging

Microscopic imaging provides a straightforward approach to deepen our understanding of cellular events. While the resolution of optical microscopes is generally limited to 200-300nm due to the diffraction limit, there has been ever growing interest in studying cells at the sub-100nm regime. By exploiting the short wavelength, long penetration depth and elemental specificity of X-rays, synchrotron-based X-ray microscopy (XRM) has demonstrated its power in exploring the structure and function of cells at the nanometer resolution. Here we summarize recent advances in using XRM for imaging ultrastructure of organelles and specific biomolecular locations in cells, and provide a perspective on potentials and applications of XRM.

Nanodiamond autophagy inhibitor allosterically improves the arsenical-based therapy of solid tumors

Arsenic trioxide (ATO) is a successful chemotherapeutic drug for blood cancers via selective induction of apoptosis; however its efficacy in solid tumors is limited. Here we repurpose nanodiamonds (NDs) as a safe and potent autophagic inhibitor to allosterically improve the therapeutic efficacy of ATO-based treatment in solid tumors. We find that NDs and ATO are physically separate and functionally target different cellular pathways (autophagy vs. apoptosis); whereas their metabolic coupling in human liver carcinoma cells remarkably enhances programmed cell death. Combination therapy in liver tumor mice model results in ~91% carcinoma decrease as compared with ~28% without NDs. Treated mice show 100% survival rate in 150 days with greatly reduced advanced liver carcinoma-associated symptoms, and ~80% of post-therapy mice survive for over 20 weeks. Our work presents a novel strategy to harness the power of nanoparticles to broaden the scope of ATO-based therapy and more generally to fight solid tumors.Arsenic trioxide (ATO) based therapy in solid cancers is limited. Here they repurpose nanodiamonds (NDs) as a safe and potent autophagic inhibitor to improve the efficacy of ATO-based treatment in solid tumors and show the combination therapy to work better in orthotopic liver cancer model.