Producing anti-inflammatory macrophages by nanoparticle-triggered clustering of mannose receptors.

Macrophages are highly plastic cells that can either mediate or suppress inflammation, depending on their cellular phenotype and cytokine secretion. Inducing macrophages from an inflammatory ('M1') to anti-inflammatory ('M2') phenotype has significant implications for the treatment of inflammatory diseases and regeneration of injured tissues. Although certain cytokines, such as interleukin-4 and -13, are known to induce this phenotypic switch, their therapeutic use in vivo has both safety and efficacy concerns. Here, we demonstrate an alternative approach to change macrophage phenotype from M1 to M2, through inducing the clustering of mannose receptors (MR) on the cell surface, by using carbohydrate-presenting substrates. We prepared and screened glucomannan-decorated silicon oxide of different sizes ranging from 10 to 1000 nm, and identified one type (KSiNP30) that could potently induce MR clustering on macrophages and thereby stimulated the cells into an M2 phenotype - as an unexpected consequence of MR activation. Further administration of KSiNP30 in a murine model of inflammatory bowel disease efficiently alleviated the colitis symptoms, indicating the translational potential of our finding for therapeutic applications. In summary, we report for the first time an approach to modulate cellular immune responses by manipulating the assembly of cell-surface receptors, without the aid of cytokines. Our approach may provide insights for the development of new anti-inflammatory therapies.

Theoretical study on the structural and antioxidant properties of some recently synthesised 2,4,5-trimethoxy chalcones.

The free radical scavenging activity of a series of 2,4,5-trimethoxy chalcones has been computationally explored using the density functional theory (DFT) method. Three potential working mechanisms, hydrogen atom transfer (HAT), stepwise electron transfer proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) have been investigated. The physiochemical parameters including O-H bond dissociation enthalpy (BDE), ionisation potential (IP), proton dissociation enthalpy (PDE), proton affinity (PA) and electron transfer enthalpy (ETE) have been calculated in gas phase and solvents. The order of antioxidant efficiencies predicted theoretically in this work is in good agreement with that reported by experimental results. The results obtained demonstrate that HAT would be the most favourable mechanism in the gas and benzene phases, whereas the SPLET mechanism is the thermodynamically preferred pathway in polar media. In addition, the importance of the A-ring on the radical scavenging capabilities of chalcones was also confirmed.

Density functional theory study of the structure-antioxidant activity of polyphenolic deoxybenzoins.

Quantum chemical calculations based on the density functional theory (DFT) have been employed to study the relationship between the structure and the antioxidant activity of four polyphenolic deoxybenzoins (DOBs) in solvents and the gas phase. The three main working mechanisms, H-atom transfer (HAT), single electron transfer-proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) have been investigated. The calculated results closely matched experimental values. The results obtained prove that for the HAT mechanism, the most efficient system possessed ortho-dihydroxy functionality. The results suggested that HAT would be the most favourable mechanism for explaining the radical-scavenging activity of polyphenolic DOBs in the gas phase, whereas the SPLET mechanism is the thermodynamically favourable pathway in polar solvents.