Targets for Macrophage-targeted Drug Delivery

Phagocytosis receptors which are located in large number on the surface of the macrophages. These receptors reflect the physiological function of macrophages and are used to internalize pathogens in macrophages. Therefore, Those receptors are optimal structures for a macrophage-targeted therapy. Equipped with a team of seasoned scientists with a powerful Platform designed specifically to meet very challenging requirements in macrophage development, Creative Biolabs offers fast and reliable support for choosing the most suitable target for Macrophage-targeted Drug Delivery System Development.


Targets for Macrophage-targeted Drug Delivery

The mannose receptors are highly expressed on macrophages. They recognize mannose and fucose glycoconjugates from the surfaces of a broad pathogen group of microscopic pathogens. The mannose-binding protein is composed of an extracellular fraction represented by lectin-like carbohydrate-binding groups and a cytoplasmic group critically involved in the cytoskeleton remodeling during endocytosis. Because of the broad structures recognized by this structure, manose receptors have been successfully used as a macrophage target receptor for oligomannose-coated liposomes in gastric cancer for targeted therapy of liposomal delivery to alveolar macrophages.

Macrophage targeting strategies of mannose receptors. Fig.1 Macrophage targeting strategies of mannose receptors. (Jahagirdar, 2019)

Scavenger receptors are a broad group of transmembrane receptors that recognize a variety of structures as low-density lipoprotein (LDL), phosphatidylserine, polyanionic ligands, chemically modified proteins unopsonized materials and negatively charged nanoparticles. Macrophage scavenger receptor class A is thought to be one of the main receptors involved in foam cell formation, mediating the influx of lipids into the macrophages.

Scavenger receptor family members with proposed roles in atherosclerosis.Fig.2 Scavenger receptor family members with proposed roles in atherosclerosis. (Moore, 2006)

TLRs are an important family of receptors that constitute the first line of defense system against microbes. TLRs are mainly expressed on immune cells such as monocytes, macrophages, and dendritic cells (DCs). The overactivation of TLRs in these cells can cause inflammation, which is a cause of various diseases. The on-target delivery of drugs to activate or inhibit the key factors may result in a cure.

Members of TLRs family and their location. Fig.3 Members of TLRs family and their location. (El-Zayat, 2019)

Generally called biological response modifiers, β-Glucans are now recognized as anti-tumor and anti-infective drugs. Macrophages and dendritic cells have typical recognition receptors (PRRs) that detect innately non-self molecules. Since β-glucans cannot directly penetrate cell membrane because of their large size, β-glucans might act as en-associated molecular patterns (PAMPs) and are recognized by PRRs. Dectin-1 and TLR might be the major PRRs for β-glucans. They might induce signaling cascade and activate immune cells upon binding with β-glucan.

The uptake and subsequent actions of β-glucan on immune cells. Fig.4 The uptake and subsequent actions of β-glucan on immune cells. (Chan, 2009)

Tumor-associated macrophages (TAMs) facilitate cancer progression by promoting tumor invasion, angiogenesis, metastasis, inflammatory responses, and immunosuppression. The folate receptor (FR) family consists of four members, including FRα, FRβ, FRγ and FRδ. FRα and FRβ, which are attached to the cell membrane through glycosylphosphatidylinositol (GPI) anchors, are overexpressed in tumor cells and TAMs, respectively. Accumulated evidence has revealed that FRβ is an attractive target for TAM-selective delivery.

The Folate receptor conjugates and their role in targeted cancer therapy. Fig.5 The Folate receptor conjugates and their role in targeted cancer therapy. (Vivek, 2017)

Macrophage-targeted Drug Delivery System Development Service at Creative Biolabs

Creative Biolabs combine deep, industry-leading expertise with an innovative Macrophage Therapeutics Development Platform to help our global clients' macrophage-targeted drug delivery system development projects. By leveraging the wealth of information that we have on macrophage-targeted drug delivery system development, we can help our clients with their study and suggest suitable receptors as targets for drug delivery.

R&D scientific team at Creative Biolabs is an expert in macrophage-targeted drug delivery system development and is happy to assist clients based on their requirements. We provide efficiencies with shorter timelines to accelerate our clients’ macrophage development projects. For more information, please feel free to contact us and further discuss with our scientists.

References

  1. Jahagirdar, P.; et al. Mannose receptor and targeting strategies. InTargeted intracellular drug delivery by receptor mediated endocytosis. 2019, 433-456. Springer, Cham.
  2. Moore, K.J.; Freeman, M.W. Scavenger receptors in atherosclerosis: beyond lipid uptake. Arteriosclerosis, thrombosis, and vascular biology. 2006, 26(8):1702-11.
  3. El-Zayat, S.R.; et al. Toll-like receptors activation, signaling, and targeting: an overview. Bulletin of the National Research Centre. 2019, 43(1):1-2.
  4. Chan, G.C.; et al. The effects of β-glucan on human immune and cancer cells. Journal of hematology & oncology. 2009, 2(1):1-1.
  5. Vivek, R.; et al. Targeted nanotherapeutics based on cancer biomarkers. InMultifunctional Systems for Combined Delivery, Biosensing and Diagnostics. 2017, pp. 229-244. Elsevier.

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