Chenchen Bao

The immunotoxicity of graphene oxides and the effect of PVP-coating

Graphene oxide (GO) immunotoxicity is not clarified well up to date. Herein we reported the effects of GOs with and without polyvinylpyrrolidone (PVP) coating on human immune cells such as dendritic cells (DCs), T lymphocytes and macrophages. Human immune cells such as dendritic cells (DCs), T lymphocytes and macrophages were isolated from health donated bloods, PVP-coating GO (PVP-GO) exhibited lower immunogenicity compared with pure GO on the aspect of inducing differentiation and maturation of dendritic cells (DCs), the levels of secreted TNF-α and IL-1β had no obvious difference between two groups, yet the secretion of IL-6 remained in PVP-coating GO group. In addition, PVP-coating GO delayed significantly the apoptotic process of T lymphocytes, at the same time, and exhibited anti-phagocytosis ability against macrophages and markedly enhanced the physiological activity of macrophages. In conclusion, PVP-coating GO possesses good immunological biocompatibility and immunoenhancement effects in vitro, and is likely to be an available candidate of immunoadjuvant in the future.

Gold nanoprisms as optoacoustic signal nanoamplifiers for in vivo bioimaging of gastrointestinal cancers.

Early detection of cancer greatly increases the chances of a simpler and more effective treatment. Traditional imaging techniques are often limited by shallow penetration, low sensitivity, low specificity, poor spatial resolution or the use of ionizing radiation. Hybrid modalities, like optoacoustic imaging, an emerging molecular imaging modality, contribute to improving most of these limitations. However, this imaging method is hindered by relatively low signal contrast. Here, gold nanoprisms (AuNPrs) are used as signal amplifiers in multispectral optoacoustic tomography (MSOT) to visualize gastrointestinal cancer. PEGylated AuNPrs are successfully internalized by HT-29 gastrointestinal cancer cells in vitro. Moreover, the particles show good biocompatibility and exhibit a surface plasmon band centered at 830 nm, a suitable wavelength for optoacoustic imaging purposes. These findings extend well to an in vivo setting, in which mice are injected with PEGylated AuNPrs in order to visualize tumor angiogenesis in gastrointestinal cancer cells. Overall, both our in vitro and in vivo results show that PEGylated AuNPrs have the capacity to penetrate tumors and provide a high-resolution signal amplifier for optoacoustic imaging. The combination of PEGylated AuNPrs and MSOT represents a significant advance for the in vivo imaging of cancers.

In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models

Up to now, functionalized gold nanoparticles have been optimized as an effective intracellular in vitro delivery vehicle for siRNAs to interfere with the expression of specific genes by selective targeting, and provide protection against nucleases. Few examples however of suchlike in vivo applications have been described so far. In this study, we report the use of siRNA/RGD gold nanoparticles capable of targeting tumor cells in a lung cancer syngeneic orthotopic murine model. Therapeutic RGD-nanoparticle treatment resulted in successful targeting evident from significant c-myc oncogene down-regulation followed by tumor growth inhibition and prolonged survival of lung tumor bearing mice, possibly via αvβ3 integrin interaction. Our results suggest that RGD gold nanoparticles-mediated delivery of siRNA by intratracheal instillation in mice leads to successful suppression of tumor cell proliferation and respective tumor size reduction. These results reiterate the capability of functionalized gold nanoparticles for targeted delivery of siRNA to cancer cells towards effective silencing of the specific target oncogene. What is more, we demonstrate that the gold-nanoconjugates trigger a complex inflammatory and immune response that might promote the therapeutic effect of the RNAi to reduce tumor size with low doses of siRNA.

Anti-HIF-1α antibody-conjugated pluronic triblock copolymers encapsulated with Paclitaxel for tumor targeting therapy

Targeted uptake of nanoscale controlled release polymer micelles encapsulated with drugs represents a potential powerful therapeutic technology. Herein we reported the development of anti-HIF-1alpha antibody-conjugated unimolecular polymer nano micelles filled with Paclitaxel for cancer targeting therapy. Pluronic triblock copolymers(Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), PEO-block-PPO-block-PEO) P123 were functionalized with terminal carboxylic groups, and were characterized by infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA), and differential scanning calorimetric (DSC). The amphiphilic copolymer nano micelles encapsulated with Paclitaxel were fabricated by self-assembly means, and then were conjugated with anti-HIF-1alpha antibody, the resultant anti-HIF-1alpha conjugated nano micelles filled with PTX (anti-HIF-1alpha-NMs-PTX nanocomposites) were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM), and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells, these treated cells were analyzed by MTT and cell-ELISA. The nanocomposites composed of anti-HIF-1alpha conjugated nano micelles filled with CdTe quantum dots were also prepared, and incubated with stomach cancer MGC-803 cells and HDF fibroblast cells for 24 h, then were observed by fluorescent microscope. Results showed that the anti-HIF-1alpha-NMs-PTX nanocomposites were successfully prepared, bound with stomach cancer MGC-803 cells specifically, were internalized, and released PTX inside cancer cells, and selectively killed cancer cells. In conclusion, unique anti-HIF-1alpha antibody-conjugated nano micelles filled with Paclitaxel can target and selectively kill cancer cells with over-expression of HIF-1alpha, and has great potential in clinical tumor targeting imaging and therapy.

A prototype of giant magnetoimpedance-based biosensing system for targeted detection of gastric cancer cells.

A targeted detection of gastric cancer cells is achieved by combining the giant magnetoimpedance (GMI)-based biosensing system and RGD-4C peptide coupled, chitosan covered superparamagnetic iron oxide particles (RGD-Fe(3)O(4)@chitosan). The micro-patterned GMI sensor for targeted detection is made of Co-based ribbon and fabricated by micro electromechanical system (MEMS) technology. Functionalized nanoparticles were designed by coating Fe(3)O(4) with chitosan and conjugating with RGD-4C peptides. The targeted cells were trickled down into the detection area of the system. The detection of each sample is carried out in ten-fold manner and average value is taken as the final result. This system can identify the differences between targeted cells and non-targeted cells. It is of considerable interest due to its potential application in the biomedical field of various specific detections.

Antibody–drug gold nanoantennas with Raman spectroscopic fingerprints for in vivo tumour theranostics

Inspired by the ability of SERS nanoantennas to provide an integrated platform to enhance disease targeting in vivo, we developed a highly sensitive probe for in vivo tumour recognition with the capacity to target specific cancer biomarkers such as epidermal growth factor receptors (EGFR) on human cancer cells and xenograft tumour models. Here, we used ~90nm gold nanoparticles capped by a Raman reporter, encapsulated and entrapped by larger polymers and a FDA antibody-drug conjugate - Cetuximab (Erbitux®) - that specifically targets EGFR and turns off a main signalling cascade for cancer cells to proliferate and survive. These drug/SERS gold nanoantennas present a high Raman signal both in cancer cells and in mice bearing xenograft tumours. Moreover, the Raman detection signal is accomplished simultaneously by extensive tumour growth inhibition in mice, making these gold nanoantennas ideal for cancer nanotheranostics, i.e. tumour detection and tumour cell inhibition at the same time.

Giant magnetoimpedance-based microchannel system for quick and parallel genotyping of human papilloma virus type 16/18

Quick and parallel genotyping of human papilloma virus (HPV) type 16/18 is carried out by a specially designed giant magnetoimpedance (GMI) based microchannel system. Micropatterned soft magnetic ribbon exhibiting large GMI ratio serves as the biosensor element. HPV genotyping can be determined by the changes in GMI ratio in corresponding detection region after hybridization. The result shows that this system has great potential in future clinical diagnostics and can be easily extended to other biomedical applications based on molecular recognition.

HER2 monoclonal antibody conjugated RNase-A-associated CdTe quantum dots for targeted imaging and therapy of gastric cancer

Successful development of safe and effective nanoprobes for targeted imaging and selective therapy of in-situ gastric cancer is a great challenge. Herein, one kind of multifunctional HER2 monoclonal antibody conjugated RNase A-associated CdTe quantum dot cluster (HER2-RQDs) nanoprobes was prepared, its cytotoxicity was evaluated. Subcutaneous gastric cancer nude mouse models and in-situ gastric cancer SCID mouse models were established, and were intravenously injected HER2-RQDs nanoprobes, the bio-distribution and therapeutic effects of HER2-RQDs in vivo were evaluated. Results showed that HER2-RQDs nanoprobes could selectively kill gastric cancer MGC803 cells, could target imaging subcutaneous gastric cancer cells at 3 h post-injection, and in-situ gastric cancer cells at 6 h post-injection, and could inhibit the growth of gastric cancer tissues and extended survival time of gastric cancer bearing mouse models, which is closely associated with destroying functional RNAs in cytoplasm by RNase A released from HER2-RQDs nanoprobes, preventing protein synthesis and inducing cell apoptosis. High-performance HER2-RQDs nanoprobes exhibit great potential in applications such as in-situ gastric cancer targeted imaging, and selective therapy in the near future.

CD44v6 Monoclonal Antibody-Conjugated Gold Nanostars for Targeted Photoacoustic Imaging and Plasmonic Photothermal Therapy of Gastric Cancer Stem-like Cells

Developing safe and effective nanoprobes for targeted imaging and selective therapy of gastric cancer stem cells (GCSCs) has become one of the most promising anticancer strategies. Herein, gold nanostars-based PEGylated multifunctional nanoprobes were prepared with conjugated CD44v6 monoclonal antibodies (CD44v6-GNS) as the targeting ligands. It was observed that the prepared nanoprobes had high affinity towards GCSC spheroid colonies and destroyed them completely with a low power density upon near-infrared (NIR) laser treatment (790 nm, 1.5 W/cm2, 5 min) in vitro experiment. Orthotopic and subcutaneous xenografted nude mice models of human gastric cancer were established. Subsequently, biodistribution and photothermal therapeutic effects after being intravenously injected with the prepared nanoprobes were assessed. Photoacoustic imaging revealed that CD44v6-GNS nanoprobes could target the gastric cancer vascular system actively at 4 h post-injection, while the probes inhibited tumor growth remarkably upon NIR laser irradiation, and even extended survivability of the gastric cancer-bearing mice. The CD44v6-GNS nanoprobes exhibited great potential for applications of gastric cancer targeted imaging and photothermal therapy in the near future.

BRCAA1 monoclonal antibody conjugated fluorescent magnetic nanoparticles for in vivo targeted magnetofluorescent imaging of gastric cancer

BackgroundGastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. How to recognize early gastric cancer cells is still a great challenge for early diagnosis and therapy of patients with gastric cancer. This study is aimed to develop one kind of multifunctional nanoprobes for in vivo targeted magnetofluorescent imaging of gastric cancer.MethodsBRCAA1 monoclonal antibody was prepared, was used as first antibody to stain 50 pairs of specimens of gastric cancer and control normal gastric mucous tissues, and conjugated with fluorescent magnetic nanoparticles with 50 nm in diameter, the resultant BRCAA1-conjugated fluorescent magnetic nanoprobes were characterized by transmission electron microscopy and photoluminescence spectrometry, as-prepared nanoprobes were incubated with gastric cancer MGC803 cells, and were injected into mice model loaded with gastric cancer of 5 mm in diameter via tail vein, and then were imaged by fluorescence optical imaging and magnetic resonance imaging, their biodistribution was investigated. The tissue slices were observed by fluorescent microscopy, and the important organs such as heart, lung, kidney, brain and liver were analyzed by hematoxylin and eosin (HE) stain method.ResultsBRCAA1 monoclonal antibody was successfully prepared, BRCAA1 protein exhibited over-expression in 64% gastric cancer tissues, no expression in control normal gastric mucous tissues, there exists statistical difference between two groups (P < 0.01). The BRCAA1-conjugated fluorescent magnetic nanoprobes exhibit very low-toxicity, lower magnetic intensity and lower fluorescent intensity with peak-blue-shift than pure FMNPs, could be endocytosed by gastric cancer MGC803 cells, could target in vivo gastric cancer tissues loaded by mice, and could be used to image gastric cancer tissues by fluorescent imaging and magnetic resonance imaging, and mainly distributed in local gastric cancer tissues within 12 h post-injection. HE stain analysis showed that no obvious damages were observed in important organs.ConclusionsThe high-performance BRCAA1 monoclonal antibody-conjugated fluorescent magnetic nanoparticles can target in vivo gastric cancer cells, can be used for simultaneous magnetofluorescent imaging, and may have great potential in applications such as dual-model imaging and local thermal therapy of early gastric cancer in near future.