Hypoxia-degradable and long-circulating zwitterionic phosphorylcholine-based nanogel for enhanced tumor drug delivery

Tumor microenvironment has been widely utilized for advanced drug delivery in recent years, among which hypoxia-responsive drug delivery systems have become the research hotspot. Although hypoxia-responsive micelles or polymersomes have been successfully developed, a type of hypoxia-degradable nanogel has rarely been reported and the advantages of hypoxia-degradable nanogel over other kinds of degradable nanogels in tumor drug delivery remain unclear. Herein, we reported the synthesis of a novel hypoxia-responsive crosslinker and the fabrication of a hypoxia-degradable zwitterionic poly(phosphorylcholine)-based (

The cytotoxic and mechanistic effects of aaptamine on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common form of cancer and the third most frequent cause of cancer-associated mortality worldwide. We isolated aaptamine from the marine sponge Aaptos, and synthesized derivatives of this compound. Aaptamine and synthetic derivatives displayed various biological activities. This represents the first account of studies on the effects of aaptamine and its derivatives in hepatocarcinogenesis. In this study, Cell Counting Kit (CCK8) was used to evaluate the anti-proliferative effect of aaptamine on HCC in vitro. Additionally, a subcutaneous xenograft model was used to determine if aaptamine could inhibit hepatocellular carcinoma in vivo. We also used RT-PCR and Western blot to analyze the mechanisms behind these effects. Our results showed that aaptamine has anti-proliferation effects on the cell lines LM3 and HepG2. Aaptamine also suppressed the colony-formation ability of HCC cells. We found that aaptamine treatment led to cell cycle arrest in HCC cells, reduced the expression of SOX9 and CDK2. Significant anti-tumor effects were observed in aaptamine-administered tumor-bearing mice as compared to controls. However, structural changes made to aaptamine yielded two derivatives for which all the effects listed above were considerably reduced as compared to the original compound aaptamine. In conclusion, aaptamine is demonstrated for the first time to inhibit liver cancer progression. The aaptamine-induced cell cycle arrest was associated with the increased binding of p21 to Cdk2-cyclin D/E complexes, inhibition of Cdk2 kinase activity in HCC cells. Furthermore, aaptamine appears to be a promising and efficient treatment of liver cancer HCC-LM3 in vivo. We have also uncovered structural changes that might affect the biological activity. The work provides a promising drug candidate for HCC treatment.

Layer-dependent electrical and optoelectronic responses of ReSe2 nanosheet transistors.

The ability to control the appropriate layer thickness of transition metal dichalcogenides (TMDs) affords the opportunity to engineer many properties for a variety of applications in possible technological fields. Here we demonstrate that band-gap and mobility of ReSe2 nanosheet, a new member of the TMDs, increase when the layer number decreases, thus influencing the performances of ReSe2 transistors with different layers. A single-layer ReSe2 transistor shows much higher device mobility of 9.78 cm(2) V(-1) s(-1) than few-layer transistors (0.10 cm(2) V(-1) s(-1)). Moreover, a single-layer device shows high sensitivity to red light (633 nm) and has a light-improved mobility of 14.1 cm(2) V(-1) s(-1). Molecular physisorption is used as "gating" to modulate the carrier density of our single-layer transistors, resulting in a high photoresponsivity (Rλ) of 95 A W(-1) and external quantum efficiency (EQE) of 18 645% in O2 environment. This work highlights the fact that the properties of ReSe2 can be tuned in terms of the number of layers and gas molecule gating, and single-layer ReSe2 with appropriate band-gap is a promising material for future functional device applications.

Fluorescent carbon dots and the application in biomedicine / 药学学报

As a new type of carbon nanomaterials, fluorescent carbon dots (fluorescent CDs) have many advantages when compared with the traditional fluorescent probes. They are photoluminescence stable and resistance to photo bleaching. Moreover, they are excellent in biocompatibility, low-toxic and easy to modify. All these above make them a promising optical image material as a probe in optical image. This article reviews structure, the common carbon sources, the preparation methods, and the light-emitting principles of the carbon dots. We also introduce the research progress of fluorescent carbon dots in biomedicine, and the problems need to be resolved in the study of fluorescent CDs.

Fluorescent carbon dots and the application in biomedicine / 药学学报

As a new type of carbon nanomaterials, fluorescent carbon dots (fluorescent CDs) have many advantages when compared with the traditional fluorescent probes. They are photoluminescence stable and resistance to photo bleaching. Moreover, they are excellent in biocompatibility, low-toxic and easy to modify. All these above make them a promising optical image material as a probe in optical image. This article reviews structure, the common carbon sources, the preparation methods, and the light-emitting principles of the carbon dots. We also introduce the research progress of fluorescent carbon dots in biomedicine, and the problems need to be resolved in the study of fluorescent CDs.

A cascade targeting strategy for brain neuroglial cells employing nanoparticles modified with angiopep-2 peptide and EGFP-EGF1 protein.

Targeted drug delivery to selected brain cell types is a crucial step in enhancing therapeutic effects while limiting side effects in non-target cells. Here we report on the development and evaluation of a new cascade targeting delivery system that employs PEG-PCL nanoparticles modified with both an angiopep-2 peptide and a EGFP-EGF1 protein for precise targeting of brain neuroglial cells. Angiopep-2 penetrates the blood-brain barrier and EGFP-EGF1 binds neuroglial cells, providing the system with two stages of targeting. In vitro studies demonstrated that both bEnd.3 cells and neuroglial cells had a higher uptake of angiopep-2 and EGFP-EGF1 conjugated nanoparticles (AENP) as compared to unmodified nanoparticles. Ex vivo imaging showed that AENP had higher accumulation in the brain over unmodified nanoparticles and EGFP-EGF1 modified nanoparticles. Fluorescent in situ hybridization of brain slides demonstrated that AENP co-localized with neuroglial cells. Transmission electron microscopy further showed that AENP could target and enter neuroglial cells. This newly developed cascade targeting delivery system that precisely targets neuroglial cells has great potential in the diagnosis and treatment of neuroglial related diseases. Replacing EGFP-EGF1 and angiopep-2 with other ligands may extend the utility of the system to diagnose and treat organ diseases beyond brain.

Vascular effect of hydroxyl-safflor yellow A and underlying mechanism / 上海第二医科大学学报

Objective To investigate the vascular effect of hydroxyl-safflor yellow A(HSYA) on rat thoracic aorta and its underlying mechanism. Methods The tension of isolated thoracic aorta rings of rats perfused with different concentrations of HSYA(1?10-6-1?10-4 mol/L) was measured using organ bath technique.The effects of HSYA on the vasocontraction induced by cumulative phenylephrine(PE)(1?10-6-1?10-4 mol/L),KCl(6?10-2 mol/L) and CaCl2(1?10-5-3?10-3 mol/L) were recorded respectively. Results HSYAcaused a concentration-dependent anti-contraction effects by KCl or PE in endothelium-intact and endothelium-denuded aortic rings.HSYA inhibited the CaCl2-induced contraction and downward shifted concentration-response curve of aortic rings.HSYA+HP resulted in more significant anti-contraction effect than single use of HSYA(P0.05).There were significant differences in anti-contraction effect between HSYA+RR and RR or HSYA(P