DHMEQ-Expressed Exosome Modification Service

DHMEQ (Dehydroxymethylepoxyquinomicin) can be used as a pretreatment for systemically administered exosomal agents, facilitating in vivo circulation and delivery of exosome carrier systems by down-regulating macrophage phagocytosis and digestion of exosomes. Creative Biolabs has a comprehensive exosome research platform that provides exosome functional investigation services to help DHMEQ intervention-induced exosome evasion phagocytosis.

DHMEQ Overview

DHMEQ is a novel small molecule NF-kB (nuclear factor κB) inhibitor synthesized by structural modification of antibiotics with anti-cancer and anti-inflammatory activity. Extensive testing in animal models of various diseases has demonstrated its broad-spectrum efficacy in the treatment of solid tumors, hematological malignancies, arthritis, intestinal ischemia, and atherosclerosis. Of greater interest is that DHMEQ induces prolongation of the circulating half-life of systemically administered exosomes by down-regulating macrophage-mediated phagocytosis.

Fig.1 Molecular design of DHMEQ based on an antibiotic epoxyquinomicin C. (Ma, 2021)

DHMEQ Induces Exosome Evasion of Phagocytosis

DHMEQ, a novel anti-inflammatory drug, is able to exert anti-inflammatory effects by inhibiting the activation of the NF-κB signaling pathway as well as modulating macrophage-mediated phagocytosis. Macrophages are vital immune cells in the immune system, which play an active role in the phagocytosis of microorganisms and waste products such as cellular debris. During the immune response, macrophages are able to secrete a variety of inflammatory factors and cytokines, including TNF-α, IL-6, and IL-1β, which cause tissue damage and inflammatory responses. DHMEQ down-regulates macrophage-mediated phagocytosis mainly in the following ways.

Inhibition of macrophage phagocytosis: DHMEQ can inhibit macrophage phagocytosis by inhibiting the NF-κB signaling pathway, reducing the phagocytosis and digestion of microorganisms and waste by macrophages. Unlike other NF-κB inhibitors that target the phosphorylation level of IκBα, DHMEQ has been identified to target the nuclear translocation of p65, a component of NF-κB, by covalently modifying specific cysteine residues in p65 and other Rel homologous proteins in a 1:1 stoichiometric ratio.
Inhibition of macrophage surface receptor expression: receptors on the surface of macrophages are important for the phagocytosis of microorganisms and cellular waste. DHMEQ can inhibit the expression of macrophage surface receptors, which in turn affects phagocytosis. For example, DHMEQ can reduce the expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in macrophages, weakening their response to external stimulation.
Reduced cytoskeleton stability: DHMEQ can reduce the stability of the macrophage cytoskeleton, which in turn affects the phagocytic function of the cells. DHMEQ can reduce the stability of the cytoskeleton by inhibiting the polymerization of microtubule proteins, which in turn reduces the phagocytic function of macrophages.

Fig.2 Signaling pathway for NF-κB activation and inhibition by DHMEQ. (Ma, 2021)

DHMEQ can down-regulate macrophage-mediated phagocytosis through various mechanisms including inhibition of the NF-κB signaling pathway, reduction of macrophage surface receptor expression, and reduction of cytoskeleton stability. This effect may be beneficial for improving the targeted delivery performance of systemically administered exosome therapies and has potential applications. Creative Biolabs provides research services on DHMEQ treatment-induced exosome evasion phagocytosis, contributing to enhancing the application utility of exosome delivery platforms. Please contact us for a customized solution.

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