Switching macrophages from a pro-tumor type to an anti-tumor state is a promising strategy for cancer immunotherapy. Existing agents, many derived from bacterial components, have safety or specificity concerns. Here, we postulate that the structures of the bacterial signals can be mimicked by using non-toxic biomolecules of simple design. Based on bioactivity screening, we devise a glucomannan polysaccharide with acetyl modification at a degree of 1.8 (acGM-1.8), which specifically activates toll-like receptor 2 (TLR2) signaling and consequently induces macrophages into an anti-tumor phenotype. For acGM-1.8, the degree of acetyl modification, glucomannan pattern, and acetylation-induced assembly are three crucial factors for its bioactivity. In mice, intratumoral injection of acGM-1.8 suppresses the growth of two tumor models, and this polysaccharide demonstrates higher safety than four classical TLR agonists. In summary, we report the design of a new, safe, and specific TLR2 agonist that can generate macrophages with strong anti-tumor potential in mice.
BackgroundFunctional polysaccharides can be derived from plants (including herbs), animals and microorganisms. They have been widely used in a broad of biomedical applications, such as immunoregulatory agents or drug delivery vehicles. In the past few years, increasing studies have started to develop natural polysaccharides-based biomaterials for various applications in tissue engineering and regenerative medicine.Main bodyWe discuss in this article the emerging applications of natural polysaccharides—particularly those derived from Chinese medicine—for wound healing. First, we introduce natural polysaccharides of three natural sources and their biological activities. Then, we focus on certain natural polysaccharides with growth factor-binding affinities and their inspired polymeric tools, with an emphasis on how these polysaccharides could possibly benefit wound healing. Finally, we report the latest progress in the discovery of polysaccharides from Chinese medicinal herbs with identified activities favouring tissue repair.ConclusionNatural polysaccharides with clearly elucidated compositions/structures, identified cellular activities, as well as desirable physical properties have shown the potential to serve as therapeutic tools for tissue regeneration.
HEPES is not suitable for fluorescence detection of HClO because it can be oxidized by HClO. A novel probe for HClO, which can selectively and sensitively detect HClO in absolute PBS, was developed on the basis of an oxidation reaction with an azo moiety. Furthermore, it works well in live mouse imaging.
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