Targeting Macrophage Toll-like Receptors (TLRs) for Drug Delivery
Toll-like receptors (TLRs) are widely distributed in all innate immune cells, including macrophages, and other body cells. TLR signaling dysregulation has been found to contribute to the development and progression of numerous diseases including autoimmune, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), chronic inflammatory, and infectious diseases as well as cancer. Therefore, targeting TLRs is an effective therapeutic strategy to suppress disease-associated inflammatory responses. The scientific team at Creative Biolabs has the necessary expertise and capabilities to provide overall solutions for targeting macrophage TLRs for drug delivery.
Introduction to TLRs
TLRs are an important family of receptors that recognize both invading pathogens and endogenous danger molecules derived from dying cells and damaged tissues. They play a key role in linking innate and adaptive immunity. The expression of TLR is not restricted to immune tissues but distributed in all tissues. They present on all innate immune cells including macrophages, NK cells, dendritic cells (DCs), monocytes, neutrophils as well as on adaptive immune cells and non-immune cells such as epithelial and endothelial cells and fibroblasts. There are about 10 members of the TLR family identified in humans and 13 identified in mice. TLRs trigger specific intracellular signaling pathways after recognition of microbial pathogens, which result in the release of inflammatory cytokines, chemokines, and type I interferon (IFN). Moreover, by upregulating the costimulatory molecules on antigen-presenting cells, TLRs connect the innate immune response with the adaptive immune response. Under certain conditions, these TLRs become hypofunctional or hyperfunctional, thus resulting in a disease-like condition. Therefore, various therapeutics including small-molecule drugs and recombinant therapeutic proteins targeting TLRs have been developed to treat the relevant diseases.
Fig.1 Immune responses mediated by TLR.1,2
Targeting of TLR Signaling
Inhibition of TLR signaling pathways has been predicted to be an effective therapeutic strategy to suppress disease-associated inflammatory responses. Blocking the binding of TLR ligands to the receptor and interfering with the intracellular signaling pathways to stop the signal transduction are two major strategies generally applied for TLR inhibition. Accordingly, various therapeutic agents for inhibiting TLR signaling have been developed to control excessive inflammation; they can be classified as small molecule inhibitors, antibodies, oligonucleotides, lipid-A analogs, microRNAs, and new emerging nano-inhibitors.
Targeting Macrophage TLRs for Drug Delivery at Creative Biolabs
The efficacy of a designed drug mainly depends upon the characteristics (half-life, specificity) of the drug itself and the delivery to a target site. Targeted delivery depends on the target location. It is relatively easy to target the cell surface rather than intracellular compartments. TLRs are mainly expressed on immune cells such as macrophages, and other cells. Targeting macrophage TLRs for delivery of drugs to activate or inhibit the key factors may result in a cure. By leveraging the wealth of information that we have on Macrophage-targeted Drug Delivery System Development, our multidisciplinary platform teams work together closely to address these scientific and technical challenges in the development of Macrophage-targeted Nanoparticle Drug Delivery System, Macrophage-targeted Liposome Drug Delivery System, and Macrophage-targeted Dendrimer Drug Delivery System. Experts at Creative Biolabs are happy to share our experience in targeting macrophage TLRs for drug delivery.
Creative Biolabs provides efficiencies with shorter timelines to accelerate our clients' macrophage-targeted drug delivery system development projects. For more information, please feel free to contact us and further discuss with our scientists.
References
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Gi, Mia, Wooseok Im, and Seokmann Hong. "Dendritic cells as danger-recognizing biosensors." Sensors 9.9 (2009): 6730-6751.
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Under Open Access license CC BY, without modification.
