Tianyu Du

Rapid and multimodal in vivo bioimaging of cancer cells through in situ biosynthesis of Zn&Fe nanoclusters

Early diagnosis remains highly important for efficient cancer treatment, and hence, there is significant interest in the development of effective imaging strategies. This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe2+ and Zn2+ ions into cancer cells (i.e., HeLa, U87, and HepG2 cancer cells). We found that the biocompatible metal ions Fe2+ and Zn2+ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe3O4 nanoclusters. These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging. Meanwhile, for normal cells (i.e., L02) and tissues, neither fluorescence nor any other obvious difference could be detected between preand post-injection. This multimodal bioimaging strategy based on the in situ biosynthesized Zn&Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy.

Synergistic effect of pyrroloquinoline quinone and graphene nano-interface for facile fabrication of sensitive NADH biosensor

A self-assembly composite of graphene-pyrroloquinoline quinone (PQQ) was fabricated and modified on glassy carbon electrode (GCE) for sensitive detection of nicotinamide adenine dinucleotide (NADH). Chitosan (CTS) was applied to disperse graphene to form a stable robust film on GCE. A synergistic effect between PQQ and graphene was observed during the electrocatalytic oxidation of NADH, with about 260mV reduction in the oxidation potential and 2.5-fold increase in the oxidation current compared with those on the bare GCE. The electrochemical sensors based on the modified electrodes allowed the detection of NADH with a good linear dependence from 0.32 to 220µM with a high sensitivity of 0.421µAµM-1cm-2 and a low detection limit of 0.16µM (S/N=3). It could also eliminate the interference of electroactive substances like ascorbic acid (AA), uric acid, and dopamine and its derivatives. The outstanding performances of graphene-PQQ/CTS composite capable of improving the electrical conductivity and accelerating the electron transport suggested its promising applications for design of different graphene based composites used in electrochemical sensing and energy fields.

Biosynthesized Gold Nanoclusters and Iron Complexes as Scaffolds for Multimodal Cancer Bioimaging.

Cancer treatment has a far greater chance of success if the neoplasm is diagnosed before the onset of metastasis to vital organs. Hence, cancer early diagnosis is extremely important and remains a major challenge in modern therapeutics. In this contribution, facile and new method for rapid multimodal tumor bioimaging is reported by using biosynthesized iron complexes and gold nanoclusters via simple introduction of AuCl4- and Fe2+ ions. The observations demonstrate that the biosynthesized Au nanoclusters may act as fluorescent and computed tomography probes for cancer bioimaging while the iron complexes behave as effective contrast agent for magnetic resonance imaging. The biosynthesized iron complexes and gold nanoclusters are found biocompatible in vitro (MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay) and in vivo for all the vital organs of circulatory and excretory system. These observations raise the possibility that the biosynthesized probes may find applications in future clinical diagnosis for deep seated early neoplasms by multimodal imaging.

Highly sensitive biosensor based on the synergistic effect of Fe3O4–Co3O4 bimetallic oxides and graphene

A sensitive sensor for the detection of dopamine (DA) and uric acid (UA) was fabricated by Fe3O4–Co3O4 bimetallic oxides anchored at a reduced graphene oxide (rGO) film-modified glassy carbon electrode (GCE). The Fe3O4–Co3O4 and rGO showed a synergistic effect towards the electrochemical catalytic oxidation of DA and UA, with the peak currents increased by 271.7% and 590%, respectively, when compared with those on bare GCE. The as-prepared Fe3O4–Co3O4/rGO based sensor supplied with a wide linear range from 5 × 10−7 to 1.55 × 10−3 M and a low detection limit (LOD) of 1.3 × 10−7 M (S/N = 3) for DA detection, and the linear range for UA detection was from 1.5 × 10−6 to 1.6 × 10−3 M and LOD was 1.8 × 10−7 M. In addition to the anti-interference capacity of electroactive molecules like ascorbic acid and 5-hydroxytryptamine, the sensor shows high recoveries for DA and UA detection in human serum samples, indicating that the as-prepared sensor exhibited high detection sensitivity and specificity, considerable stability and reproducibility, and excellent anti-interference capability.

In Vivo Biosynthesized Zinc and Iron Oxide Nanoclusters for High Spatiotemporal Dual-Modality Bioimaging of Alzheimer’s Disease

Alzheimers disease is still incurable and neurodegenerative, and there is a lack of detection methods with high sensitivity and specificity. In this study, by taking different month old Alzheimers mice as models, we have explored the possibility of the target bioimaging of diseased sites through the initial injection of zinc gluconate solution into Alzheimers model mice post-tail vein and then the combination of another injection of ferrous chloride (FeCl2) solution into the same Alzheimers model mice post-stomach. Our observations indicate that both zinc gluconate solution and FeCl2 solution could cross the blood-brain barrier (BBB) to biosynthesize the fluorescent zinc oxide nanoclusters and magnetic iron oxide nanoclusters, respectively, in the lesion areas of the AD model mice, thus enabling high spatiotemporal dual-modality bioimaging (i.e., including fluorescence bioimaging (FL) and magnetic resonance imaging (MRI)) of Alzheimers disease for the first time. The result presents a novel promising strategy for the rapid and early diagnosis of Alzheimers disease.

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl4, FeCl2), whereas Na2SeO3 supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.

Real-Time Multimodal Bioimaging of Cancer Cells and Exosomes through Biosynthesized Iridium and Iron Nanoclusters

Multimodal bioimaging is a powerful tool for visualizing the abnormal state at the target site of the related disease. In this study, we used multimodal imaging techniques such as computed tomography, fluorescence, and magnetic resonance imaging to improve early and precise diagnosis of tumor. Herein, we reported the facile in situ biosynthesis of iridium and iron oxide nanoclusters (NCs) in cancer cells or tumor tissue. These NCs are used as a multimodal bioimaging probe to improve the image sensitivity and specificity toward the tumor. These NCs are applied for the in vivo multimodal imaging in the form of an imaging probe capable of enhancing the sensitivity of the image and specificity toward the tumor tissue. Our observation demonstrates that highly luminescent and magnetic NCs are not only biocompatible but also tumor-targeted because NC formation does not take place in normal cells and tissues. In addition, we isolated exosomes and the biosynthesized NCs internalized within exosomes, and these exosomes can be used as cancer biomarkers.

Adjusting the Linear Range of Au-MOF Fluorescent Probes for Real-Time Analyzing Intracellular GSH in Living Cells

A series of Au-loaded metal-organic frameworks (MOFs) were synthesized in this study and further employed for real-time quantitative analysis of intracellular glutathione (GSH) level. Different linear ranges can be acquired by altering the size of gold and MOF particles, or adjusting the proportion of 2-aminoterephthalic acid/1,4-benzenedicarboxylate linkers, which is also observed on fluorescein isothiocyanate-attached Au-MOFs. Further study reveals that the flexible molecular chain of GSH with the -COOH/-NH2 and -SH terminals may readily tie on relevant gold nanoparticles through its -NH2/-COOH groups, which then restricts the intramolecular motions of fluorescence probes and thus induces marked fluorescence enhancement. On the basis of these observations, the intracellular GSH levels of different cells including L02 cells, Hela, and U87 as well as HepG2 cancer cells can be rapidly evaluated by these Au-MOF probes.

Correction to: Monitoring dynamic release of intracellular hydrogen peroxide through a microelectrode based enzymatic biosensor

The authors would like to call the reader’s attention to the fact that unfortunately Alberto Pasquarelli’s and Kay-Eberhard Gottschalk’s affiliations were wrong in the original publication.