Effect of space length of mannose ligand on uptake of mannosylated liposome in RAW 264.7 cells:In vitroandin vivostudies

Abstract

The most widely used method for increasing uptake on macrophage is specific targeting for mannose receptor (MR) presented on macrophages. Efficiency of the uptake for MR is influenced by the space length and flexibility of mannose ligand in liposome (LP). We prepared mannosylated liposomes (M-EGn-LP-ICG) encapsulated indocyanine green (ICG) with mannose ligand of various ethylene glycol units (EG), LP-ICG, and mannosylated liposome (M-LP-ICG) incorporated with p-aminophenyl-α-d-mannopyranoside. We studied the effect of space length of the mannose ligand in vitro and in vivo with prepared liposomes. A space length of two ethylene glycol units at least was needed for uptake by macrophages and the uptake was increased as the space length increased up to EG4. We measured near-infrared (NIR) fluorescence intensity by ICG and the fluorescence value of cell-associated N-(4-nitrobenzo-2-oxa-1,3-diazole) (NBD) in liposome after cellular uptake. M-EG4-LP-ICG showed lower NIR fluorescence intensity but higher NBD fluorescence value than M-LP-ICG. The result of pre-treatment with d(+)-mannose as an inhibitor showed significant decreasing in uptake of mannosylated LP-ICG but no difference in LP-ICG. These were explained that mannosylated LP-ICG was taken up by macrophages through the MR and M-EG4-LP-ICG showed more specific uptake than M-LP-ICG. We obtained images as time passed in the NIR range after intravenous administration using a Balb/c mouse with inflammatory model. The results showed high uptake in liver at early time and rapid degradation of mannosylated LP-ICG. M-EG4-LP-ICG was more selectively taken up by macrophages than M-LP-ICG.

Optimization of the Linker Length of Mannose-Cholesterol Conjugates for Enhanced mRNA Delivery to Dendritic Cells by Liposomes

“…Linker length of ligand exerted significantly effect on targeting cellular uptake ( Engel et al, 2003 ; Stefanick et al, 2013 ; Jeong et al, 2014 ). Thus, a proper linker length of the ligands was essential for effective receptor recognize and binding.…”

“…According to literatures, the length and flexibility of the space between ligand molecules and the surface of particles might be important parameters for efficient recognition of receptors ( Engel et al, 2003 ; Stefanick et al, 2013 ; Jeong et al, 2014 ). A short linker may restrict the translational freedom of ligand, while the longer one might bury a large fraction of the conjugated ligand ( Stefanick et al, 2013 ).…”

“…A short linker may restrict the translational freedom of ligand, while the longer one might bury a large fraction of the conjugated ligand ( Stefanick et al, 2013 ). The optimal linker provides a more effective ligand-receptor interaction ( Stefanick et al, 2013 ; Jeong et al, 2014 ). Thus, a rational design of the targeting LPs is crucial to enhanced mRNA delivery to DCs.…”

Internalization of Exosomes through Receptor-Mediated Endocytosis

“…Many proteins have been identified as participants in the endocytosis of exosomes (Table 1). Similar protein-protein interactions significantly contribute to recognition and endocytosis of molecules important for cellular activities pertaining to the uptake of viruses (44,77,78), liposomes (79,80), and nanoparticles (81,82). One of the many ways viruses induce internalization by the host is through apoptotic mimicry, which involves externally expressing phosphatidylserine that binds to cellular T-cell immunoglobulin mucin (TIM) receptors (78).…”

Current Comprehension of Vesicular Intercellular Signaling

“…Доля рецептора і ліганда варіює, залежно від типу першого і механізму ендоцитозу [49]. Багато білків поглинання рецепторів були ідентифіковані як учасники ендоцитозу екзосом і такі міжбілкові взаємодії роблять значний внесок у розпізнавання та ендоцитоз молекул, важливих як для клітинної активності, так і пов'язаних з проникненням вірусів [16,50,51], ліпосом [52,53] та наночастинок [54,55].…”