Silsesquioxane‐Containing Hybrid Nanomaterials: Fascinating Platforms for Advanced Applications

Silsesquioxanes (SSQs), with the general formula, (RSiO_1.5)_n—where R stands for an organic group, such as alkyl, aryl, alkoxy, or H—are a type of molecular‐level organic/inorganic hybrid silica‐based material. These materials contain reactive or nonreactive organic moieties as well as inorganic Si–O–Si frameworks. In the past few years, extensive efforts have been made using SSQs to construct multifunctional nanocomposites with suitable properties for a range of applications. In this review, the recent various applications of SSQ‐containing hybrid materials are discussed, in addition to updates of the nanocomposite applications. Various physical structures and chemical reactions in SSQ‐based hybrid nanomaterials are emphasized with regard to applications in the field of polymer nanocomposites, catalysts, adsorption, sensors, and biomedicine. This review focuses on results reported in the recent five years (2013–2018).     

Potential applications and human biosafety of nanomaterials used in nanomedicine

With the rapid development of nanotechnology, potential applications of nanomaterials in medicine have been widely researched in recent years. Nanomaterials themselves can be used as image agents or therapeutic drugs, and for drug and gene delivery, biological devices, nanoelectronic biosensors or molecular nanotechnology. As the composition, morphology, chemical properties, implant sites as well as potential applications become more and more complex, human biosafety of nanomaterials for clinical use has become a major concern. If nanoparticles accumulate in the human body or interact with the body molecules or chemical components, health risks may also occur. Accordingly, the unique chemical and physical properties, potential applications in medical fields, as well as human biosafety in clinical trials are reviewed in this study. Finally, this article tries to give some suggestions for future work in nanomedicine research. Copyright © 2017 John Wiley & Sons, Ltd.     

Advances in immunosensors for clinical applications

ABSTRACT

Immunoassay technique performs a fast, simple, reliable, and sensitive analysis of different compounds, being applied in several areas of interest such as clinical analysis for medical diagnosis, as well as in environmental analysis, and food quality control. The latest research activities in this field are represented by the attempts to achieve a low limit of detection by developing of new signal amplification strategies, eliminate the interferences, and decrease the cost of analysis.     

Superparamagnetic iron oxide magnetic nanomaterial-labeled bone marrow mesenchymal stem cells for rat liver repair after hepatectomy

Background

Superparamagnetic iron oxide magnetic nanomaterials (SPIO) are tracers used for treatment of central nervous and cardiovascular system complications in animal models. The present study investigated survival and proliferation of SPIO-labeled bone marrow mesenchymal stem cells (BMSCs) to determine their potential therapeutic value in liver repair.

Methods

Surface antigens of BMSCs were measured using flow cytometry. BMSCs viability, growth curve, and SPIO (0–100 μg/mL) labeling rate were evaluated using trypan blue staining, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and Prussian blue staining, respectively. SPIO-labeled BMSCs were transplanted via liver or spleen injection in rats undergoing 70% hepatectomy. Distribution of SPIO-labeled BMSCs in liver and spleen, and liver repair were evaluated by magnetic resonance imaging (MRI), and serum alanine aminotransferase, aspartate aminotransferase, albumin, and total bilirubin levels.

Results

CD29⁺/CD90⁺/CD45⁻ BMSCs were successfully isolated from rats. Labeling rate of SPIO in 25 μg/mLwas 94.9%. SPIO labeling did not affect BMSCs survival and proliferation. MRI showed that BMSCs colonized in the liver, whether via spleen or liver injection. Serum levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin in the transplanted rats were significantly lower than in the hepatectomy group at days 1, 3, and 7 after hepatectomy (all P < 0.05), whereas serum albumin levels were significantly higher in the transplanted rats on posthepatectomy day 3 (both P < 0.05). These indicators were not significantly different between the spleen and liver injection approaches.

Conclusions

BMSCs transplantation via liver or spleen injection could significantly accelerate liver healing. In vivo MRI of SPIO-labeled BMSCs can be used to trace real-time liver healing during clinical treatment after hepatectomy.     

基于铁死亡的癌症治疗新策略

铁死亡(ferroptosis)主要依赖于细胞内铁和脂质活性氧(L-ROS)累积所引起的细胞死亡,是一种新的调节性细胞死亡形式。自2012年首次提出以来,在生物化学、肿瘤学和材料科学研究等领域引起了广泛的关注,通过激活或抑制细胞铁死亡来干预癌症的进程成为癌症治疗的新热点,包括小分子化合物、纳米材料和基因技术等。本文主要阐述当前基于铁死亡的癌症治疗新策略、优势与局限性,期望为癌症治疗提供参考。     

Gold-based nanomaterials for the treatment of brain cancer

Brain cancer, also known as intracranial cancer, is one of the most invasive and fatal cancers affecting people of all ages. Despite the great advances in medical technology, improvements in transporting drugs into brain tissue have been limited by the challenge of crossing the blood-brain barrier (BBB). Fortunately, recent endeavors using gold-based nanomaterials (GBNs) have indicated the potential of these materials to cross the BBB. Therefore, GBNs might be an attractive therapeutic strategy against brain cancer. Herein, we aim to present a comprehensive summary of current understanding of the critical effects of the physicochemical properties and surface modifications of GBNs on BBB penetration for applications in brain cancer treatment. Furthermore, the most recent GBNs and their impressive performance in precise bioimaging and efficient inhibition of brain tumors are also summarized, with an emphasis on the mechanism of their effective BBB penetration. Finally, the challenges and future outlook in using GBNs for brain cancer treatment are discussed. We hope that this review will spark researchers’ interest in constructing more powerful nanoplatforms for brain disease treatment.     

Polyethylene glycol modification decreases the cardiac toxicity of carbonaceous dots in mouse and zebrafish models

Aim:

Carbonaceous dots (CDs), which have been used for diagnosis, drug delivery and gene delivery, are accumulated in heart at high concentrations. To improve their biocompatibility, polyethylene glycol-modified CDs (PEG-CDs) were prepared. In this study we compared the cardiac toxicity of CDs and PEG-CDs in mouse and zebrafish models.

Methods:

Mice were intravenously treated with CDs (size: 4.9 nm, 5 mg·kg⁻¹·d⁻¹) or PEG-CDs (size: 8.3 nm, 5 mg·kg⁻¹·d⁻¹) for 21 d. Their blood biochemistry indices, ECG, and histological examination were examined for evaluation of cardiac toxicity. CDs or PEG-CDs was added in incubator of cmlc2 transgenic Zebrafish embryos at 6 hpf, and the shape and size of embryos'' hearts were observed at 48 hpf using a fluorescent microscope. Furthermore, whole-mount in situ hybridization was used to examine the expression of early cardiac marker gene (clml2) at 48 hpf.

Results:

Administration of CDs or PEG-CDs in mice caused mild, but statistically insignificant reduction in serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels detected at 7 d, which were returned to the respective control levels at 21 d. Neither CDs nor PEG-CDs caused significant changes in the morphology of heart cells. Administration of CDs, but not PEG-CDs, in mice caused marked increase of heart rate. Both CDs and PEG-CDs did not affect other ECG parameters. In the zebrafish embryos, addition of CDs (20 μg/mL) caused heart development delay, whereas addition of CDs (80 μg/mL) led to heart malformation. In contrast, PEG-CDs caused considerably small changes in heart development, which was consistent with the results from the in situ hybridization experiments.

Conclusion:

CDs causes greater cardiac toxicity, especially regarding heart development. Polyethylene glycol modification can attenuate the cardiac toxicity of CDs.     

The potential health challenges of TiO2 nanomaterials

Titanium dioxide (TiO₂) nanomaterials (NMs) have found widespread applications owing to their attractive physical and chemical properties. As a result, the potential adverse impacts of nano‐TiO₂ exposure on humans have become a matter of concern. This review presents the state‐of‐the‐art advances on the investigations of the adverse effects of NMs, including the potential exposure routes of nano‐TiO₂ (e.g. respiratory system, skin absorption and digestive system), the physico‐chemical characterizations of nano‐TiO₂ (e.g. crystal structure, shape,size, zeta potential, treatment media, aggregation and agglomeration tendency, surface characteristics and coatings), risk evaluation of nanotoxicity (e.g. cytotoxicity, ecotoxicity, phototoxicity, and phytotoxicity) and potential mechanisms of adverse effects (e.g. generation of reactive oxygen species, oxidative stress and organelle dysfunction). The review aims to facilitate scientific assessments of health risks to nano‐TiO₂, which would guide the safe applications of NMs in our daily life. Copyright © 2015 John Wiley & Sons, Ltd.     

A novel assay for the quantification of internalized nanoparticles in macrophages

One of the most urgent requirements in nanotoxicology is a quantitative assessment of internalized nanomaterials in cells. We present an in vitro assay called ‘max-flat’ for the measurement of internalized particles in macrophages. Fluorescent polystyrene (PS) beads of diameters 1 µm, 500 nm, 200 nm, 100 nm and 20 nm were employed. Different concentrations of fibronectin (FN) coated substrates were tested to achieve a maximal cell spreading area and minimal nucleus height, hence ‘max-flat’. We found this cell spreading area depends on FN concentration, and it is independent of particle concentration. An optimal condition of FN was found at 2.5×10^?3 mg/ml, and it was selected for the max-flat assay to assess the internalization of PS beads. Cells under these conditions neither generate reactive oxygen species nor show noticeable differences in pro-survival/pro-apoptotic signals. Confocal images were employed for the max-flat assay and we set the interval scanning for a Z-stack as nucleus height divided by particle diameter. The max-flat assay provided a significantly higher number of internalized particles and the saturation is reached faster for nano-scale PS beads. We show how the proposed max-flat assay clearly outperform existing techniques by providing easier, more precise and far more reliable access to the number of internalized nanoparticles in macrophages.     

Are nanoparticles potential male reproductive toxicants? A literature review

The rapid advancement of nanotechnology has prompted the need to investigate the health effects of nanoparticles and nanomaterials. The current focus of health and safety investigations has targeted routes of exposure and potential deposition, translocation, and adverse effects in primary and major secondary target organs. Few studies have looked at deposition in reproductive organs, and even fewer have assessed potential adverse effects on germline cells. This review summarizes the current published research on deposition/translocation of nanoparticles to the testes and male germline cells, and the potential cytotoxic effects. Six research articles were identified. Three articles pertained to deposition/translocation of nanoparticles in the testes, two pertained to cytotoxicity of nanoparticles on male germline cells, and one study assessed deposition and bioaccumulation of nanoparticles in the testes, and potential for adverse reproductive outcomes in successive offspring. While research into the potential reproductive toxicity of nanoparticles is still in its infancy, the identified research suggests that nanoparticles cross the blood testes barrier and deposit in the testes, and that there is potential for adverse effects on sperm cells. Suggestions for future research strategies are outlined.