Synthesis of Mannose‐Cholesterol Conjugates for Targeted Liposomal Drug Delivery

Abstract

Several novel, mannose‐cholesterol conjugates for use in targeted liposomal drug delivery were synthesized via a modular strategy utilizing the Cu(I)‐catalysed Huisgen azide‐alkyne cycloaddition (“Click”) reaction. The conjugates, which were fully characterized, comprised either a single mannose unit or a trivalent mannose cluster joined to cholesterol via bifunctional PEG‐based linkers of different lengths. The neutral conjugates offer advantages over a previously reported cationic conjugate and the modular strategy employed can be readily adapted for the preparation of conjugates with alternative targeting groups.

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

“…As shown in Figure 1A , MP 100 -CH was obtained with similar procedures as described previously ( Kim et al, 2012 ; Nguyen et al, 2016 ). In brief, Diethylene glycol (5.0 eq), paratoluensulfonyl chloride (TosCl, 1.0 eq) and triethylamine (TEA, 1.1 eq) were dissolved in anhydrous dichloromethane (DCM) and stirred for 24 hours (h) at room temperature (rt).…”

Double Sequential Encrypted Targeting Sequence: A New Concept for Bone Cancer Treatment

“…One of the promising alternatives for improving the selectivity of chemotherapy is the covalent conjugation of vectorization moieties or targeting systems directly on the surface of drug‐loaded nanocarriers, with both inorganic and organic nature, as well as to free drugs generating vectorized drug conjugates. A wide variety of targeting systems, from big biomolecules like antibodies, lipoproteins, or oligonucleotide sequences to small molecules such as vitamins, sugars, or synthetic molecules, are known. These moieties are characterized by their capacity to recognize and specifically bind to membrane cell receptors which are only, or mainly, expressed by tumor cells.…”

Application of Mono‐ and Disaccharides in Drug Targeting and Efficacy

“…[39] Mannose has been used to coat liposomes as au seful ligand for delivery to cells that highly express mannose receptors. [31,[40][41][42][43] The mannose-cholesterol conjugate Man-C4-Chol (12)a nd its derivatives 13 and 14,k nown as conjugates that selectively targetm annose receptors, have been reported by severalr esearch groups in the preparation of mannose-func-tionalized cationic liposomes to achievet arget specificity ( Figure 3). [44]…”