Synthetic Siglec Ligands-Bearing Liposomes Agonist

Examples of Liposomes Bearing Siglec Ligands

Siglec ligands-bearing liposome agonist is some sort of liposome-carrying multivalent Siglec ligands on their surface.

Siglec-3 (CD33) ligands displayed on liposome

CD33 is expressed by microglia. Researchers use liposomes known as CD33L liposomes, which multivalently display CD33 glycan ligands, to interact with CD33. They found that cultured monocytic cells and microglia are more likely to be phagocytosed by CD33-dependent CD33L liposomes. Increased phagocytosis induced by treatment with CD33L liposomes depends on the ability of CD33 to bind to glycans as well as a critical intracellular signaling motif.

The mechanism of liposome bearing CD33

These effects only occur when CD33L liposomes contact CD33 trans since cis engagement occurs when lipid-linked CD33L is inserted into cells, which has the opposite impact on phagocytosis. Additionally, intracerebroventricular injection of CD33L liposomes into transgenic mice that express human CD33 in the lineage of microglial cells improves microglia phagocytosis in a CD33-dependent manner.

Fig.1 CD33L (glycan ligands of CD33) liposomes increase phagocytosis of cultured monocytic cells and microglia in a CD33-dependent manner. (Bhattacherjee, et al., 2021)

Different Classes of Liposomes Bearing Siglec Ligands

Liposome bearing Siglec-1 ligand

It has been investigated how to direct antigens to macrophages using siglec-1 ligands. In vivo, Siglec-1-expressing macrophages were targeted by liposomes containing a peptide antigen and the natural Siglec-1 ligand GM3 (Neu5Ac2-3Gal1-4Glc-ceramide), triggering a more potent immune response.

Liposome bearing Siglec-2 ligand

A lipid aglycone was used to create a synthetic mouse Siglec-2 (CD22) mimic Neu5Gc2-6Gal1-4GlcNAc with a 9-N-biphenylacetyl group, which was then combined with antigens associated with the target autoimmune disorders to generate liposomes. Human memory B cells derived from rheumatoid arthritis patients were not able to produce targeted antibodies when exposed to Neu5Ac2-6Gal1-4GlcNAc containing a 9-N-m-phenoxybenzamide, a similar lipid-linked mimetic.

Liposome bearing Siglec-3 ligand

Along with a mast cell antigen, the human Siglec-3-targeted sialomimetic was covalently joined to a lipid and included in liposomes. The antigen attached to sensitized mast cells when it was administered in a liposome, and the sialomimetic attracted inhibitory hSiglec-3 to the location, inhibited mast cell degranulation, and prevented anaphylaxis in rheumatoid arthritis patients.

Liposome bearing Siglec-7 ligand

Natural killer (NK) cells may be released from Siglec-7-mediated inhibition and be more effective at removing tumors if Siglec-7 is blocked. Siglec-7-bearing cells may be able to receive cargo when targeted by multivalent sialoglycans, and Siglec-7-bearing cells were very selectively targeted by liposomes containing the lipid-linked mimetic.

Functions of Liposomes Bearing Siglec Ligands in Biology

Sepsis, autoimmune, and allergies are a few of the illnesses that the Siglecs treat by reducing inflammation. For the purpose of particularly combating harmful inflammatory reactions caused by siglec agonism, antibodies, recombinant ligands, nanoparticles, or liposomes may be utilized. The proper Siglec interacts with synthetic Siglec ligands on liposomes or nanoparticles, causing it to cluster and, in certain cases, causing it to localize close to an activating receptor and impede its activation. For instance, the therapeutic potential of Siglec agonism was demonstrated by the induction of particular B cell populations' death by liposomes coated with antigen and CD22 ligands.

Fig.2 Mechanism of action of liposomes containing Siglec ligands. (Macauley, et al., 2014)

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References:

Bhattacherjee, A.; et al. Increasing phagocytosis of microglia by targeting CD33 with liposomes displaying glycan ligands. Journal of Controlled Release. 2021, 338, 680–693.
Macauley, M.S.; et al. SIGLEC-mediated regulation of immune cell function in disease. Nature Reviews Immunology. 2014, 14(10): 653–666.

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