Phagocytosis receptors are located in large number on the surface of macrophages. These receptors reflect the physiological function of macrophages and are used to internalize pathogens in macrophages. Therefore, those receptors are optimal structures for 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

• Mannose receptors

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.

Fig.1 The sMR induces proinflammatory activation of macrophages.^1,6

• Scavenger receptors

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.

Fig.2 The multistep leukocyte adhesion cascade.^2,6

• Toll-like receptors (TLRs)

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.

Fig.3 Members of TLRs family and their location.^3,6

• β-glucan

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.

Fig.4 The uptake and subsequent actions of β-glucan on immune cells.^4,7

• Folate receptors

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.

Fig.5 Main aspects of folate receptor signaling and C1 metabolism discussed during the meeting.^5,6

Macrophage-targeted Drug Delivery System Development Service at Creative Biolabs

Creative Biolabs is dedicated to the development of drug delivery systems targeting macrophages, providing innovative solutions for experimental research. We integrate the following technology platforms to meet experimental research needs.

Table 1 Technology platforms for macrophage-targeted drug delivery system development

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 efficiency and short timelines to accelerate our clients' macrophage development projects.

Our standardized service process framework includes:

• Requirements analysis and program design
• Carrier development and characterization
• Functional validation
• Data delivery and optimization iterations

Related Products

Our services include target vector design, drug screening, in vitro experiments, and preclinical evaluation to ensure that our clients' development process is efficient and smooth. At the same time, we are able to provide customized solutions according to the needs of different clients. On this basis, we are also proud to introduce our research products, including a variety of macrophages, assay kits and macrophage engineering products.

Below are some of our popular products. You can click to view the details. By utilizing our services and products, you will be able to accelerate the R&D process.

Service Features

Technical Uniqueness

Experienced biopharmaceutical researchers and drug development experts, as well as unique target ligand libraries and vector construction technologies.

End-to-end Services

End-to-end services from target screening to preclinical studies, with modern laboratories and equipment capable of performing a wide range of complex experiments.

Customized Services

We provide personalized services based on specific customer needs to ensure maximum relevance and application value of research results.

Scientific Resources

Learn More Macrophages in Diseases

Download Macrophage Recruitment and Chemotaxis

Learn More Development of Fine Liposome Nanoplatforms for Macrophage Clearance

Learn More Isolation and Identification of Macrophages

Q & A

Q: How is the suitability of a particular target determined? What key metrics are included in the selection criteria?

A: When selecting targets, we conduct a comprehensive evaluation based on multi-dimensional scientific rationale and research needs, including receptor expression specificity, pathologic relevance, targeting efficiency and safety, and technical feasibility.

Q: For safety assessment of targets, what methods does your company use to validate off-target effects and long-term toxicity?

A: Our safety evaluation system covers the following core aspects:

• In vitro model validation
• Preclinical animal models

References

1. van der Zande, Hendrik JP, et al. "The mannose receptor: from endocytic receptor and biomarker to regulator of (meta) inflammation." Frontiers in Immunology 12 (2021): 765034. https://doi.org/10.3389/fimmu.2021.765034
2. Patten, Daniel A., and Shishir Shetty. "More than just a removal service: scavenger receptors in leukocyte trafficking." Frontiers in Immunology 9 (2018): 423021. https://doi.org/10.3389/fimmu.2018.02904
3. El-Zayat, Salwa Refat, Hiba Sibaii, and Fathia A. Mannaa. "Toll-like receptors activation, signaling, and targeting: an overview." Bulletin of the National Research Centre 43.1 (2019): 1-12. https://doi.org/10.1186/s42269-019-0227-2
4. Chan, Godfrey Chi-Fung, Wing Keung Chan, and Daniel Man-Yuen Sze. "The effects of β-glucan on human immune and cancer cells." Journal of hematology & oncology 2 (2009): 1-11. https://doi.org/10.1186/1756-8722-2-25
5. Frigerio, Barbara, et al. "Folate receptors and transporters: biological role and diagnostic/therapeutic targets in cancer and other diseases." (2019): 1-12. https://doi.org/10.1186/s13046-019-1123-1
6. Under Open Access license CC BY 4.0, without modification.
7. Under Open Access license CC BY 2.0, without modification.