Lang Zhuo

Self-assembled micellar nanocomplexes comprising green tea catechin derivatives and protein drugs for cancer therapy

In designing drug carriers, the drug-to-carrier ratio is an important consideration because using high quantities of carriers can cause toxicity resulting from poor metabolism and elimination of the carriers1. However, these issues would be of less concern if both the drug and carrier possess therapeutic effects. (-)-Epigallocatechin-3-O-gallate (EGCG), which is a major ingredient of green tea, has been shown to possess anticancer effects2-7, anti-HIV effects8, neuroprotective effects9, DNA-protective effects10, etc. Here we show that sequential self-assembly of the EGCG derivative with anticancer proteins forms stable micellar nanocomplexes (MNCs), which have greater anticancer effects in vitro and in vivo than the free protein. The MNC is obtained by complexation of oligomerized EGCG with the anticancer protein, Herceptin, to form the core, followed by complexation of poly(ethylene glycol)-EGCG to form the shell. When injected into mice, the Herceptin-loaded MNC showed better tumour selectivity and growth reduction, and longer blood-half-life than free Herceptin.

A thixotropic nanocomposite gel for three-dimensional cell culture

Thixotropic materials, which become less viscous under stress and return to their original state when stress is removed, have been used to deliver gel-cell constructs and therapeutic agents. Here we show that a polymer-silica nanocomposite thixotropic gel can be used as a three-dimensional cell culture material. The gel liquefies when vortexed--allowing cells and biological components to be added--and resolidifies to trap the components when the shear force from spinning is removed. Good permeability of nutrients and gases through the gel allows various cell types to proliferate and be viable for up to three weeks. Human mesenchymal stem cells cultured in stiffer gels developed bone-like behaviour, showing that the rheological properties of the gel can control cell differentiation. No enzymatic, chemical, or photo-crosslinking, changes in ionic strength or temperature are required to form or liquefy the gel, offering a way to sub-culture cells without using trypsin-a protease commonly used in traditional cell culture techniques.

Imidazolium salts: a mild reducing and antioxidative reagent.

The concept of directly using imidazolium salts (IMSs) as mild reducing and antioxidative reagents was proposed and investigated. A simple and robust protocol for the synthesis of stable, ultrafine gold nanoparticles has been established using IMSs under mild conditions. IMSs showed remarkably lower toxicity but greater antioxidative power than N-acetyl-L-cystein and (-)-epigallocatechin gallate on HSC-T6 cells. These studies demonstrate that the simple and inexpensive IMSs represent a new type of antioxidant with potential biomedical applications.

Non-invasive imaging of transgenic GFP expression in neonatal mouse brain

Glial fibrillary acidic protein (GFAP) is a traditional biomarker for astrocytes of the central nervous system. In this study, non-invasive in vivo imaging of GFAP-GFP (green fluorescent protein) expression in the brain of neonatal transgenic mice is used as a novel method to investigate the relationship between the expression of the transgene at 0, 2, 4, 6 and 8 hr post-treatment in mice subjected to a single administration of 12 mg/kg of neurotoxin 1-methyl-4(2-methylphenyl)-1,2,3,6-tetrahydropyridine (2-CH3-MPTP). The GFP elevation was found to peak at 6 hr and lasted to at least 8 hr after the toxin treatment. Histological examination of fixed brain sections using immunohistochemistry (IHC) shows an increase in GFP and GFAP signal from the substantia nigra pars compacta (SNpc) and the hippocampus. The results have provided quantitative fluorescence and qualitative histological evidence for the activation of the GFAP-GFP transgene in astrocytes following neurotoxin 2-CH3-MPTP administration, suggesting that the model described here could be used to study neuronal degeneration such as Parkinsons disease and in general, developmental neurotoxicity in live animals.