Leuko-polymersomes

Abstract

Polymersomes are vesicles whose membranes are comprised of self-assembled amphiphilic block co-polymers. Synthetic control of block co-polymer chemistry provides an advantageous diversity of polymersome functions, ranging from tunable materials strength, superior encaspulation of hydrophobic and hydrophilic drugs and optical dyes, and facile functionalization. We have exploited polymersome tunability to make leuko-polymersomes: polymersomes with the adhesive properties of leukocytes. By functionalizing the terminal groups on the outer shell of the vesicle with biotin, we have used modular avidin-biotin chemistry to attach adhesion ligands that mimic the two critical adhesion pathways that leukocytes utilize to achieve adhesion in the fast fluid flow of blood vessels--selectins and integrins. We demonstrate that adhesion is specific and is supported at hydrodynamic flow rates at which leukocytes adhere. We envision the use of such particles for monitoring or treating inflammation, cancer and cardiovascular disease.

Functionalization of Block Copolymer Vesicle Surfaces

“…In contrast to previous studies, the adhesion strength did not depend on the amount of biotinylated block copolymer, but rather increased linearly with the surface-density of the binding ligand, because the flexible polymer chains are buried underneath the coat of neutravidin (Figure 3(b) and 3(c)). Under physiological flow rates, such decorated vesicles do adhere to surfaces coated with inflammatory adhesion molecules P-selectin (to which sLe x binds) and ICAM-1 [45,49], as well as to inflamed endothelium [49], indicating possible applications as a targeted drug-delivery system. Although cell-specific targeting in vitro was shown with polymersomes that were surface-modified by a biotin-streptavidin approach [20,34], such polymersomes would not be of use in vivo studies because streptavidin is known to block essential immune reactions in the human body [50].…”

“…Ligands are bound indirectly by biotin-streptavidin-biotin interactions to the polymersome surface. The modification of block copolymers with biotin has been performed either by N,N'-dicyclohexylcarbodiimide/4-(dimethylamino)pyridine-activated esterification [17,20,34,35] or by preactivation of the terminal hydroxyl functionality by tresyl chloride [44] or 4-fluoro-3-nitrobenzoic acid [36,45] and subsequent reaction with biocytin [33,36]. Both the esterification and the tresylation method resulted in a good yield of biotin modified polymer, which is essential for streptavidin and thus ligand binding after self-assembly of the polymersome.…”

Multifunctional nanoassemblies of block copolymers for future cancer therapy

“…leuko-polymersomes. Thus, functionalizing the terminal groups on the outer shell of vesicles via avidin-biotin chemistry, Hammer et al attached adhesion ligands, selectins and integrins, mimicking the two critical adhesion pathways that leukocytes utilize to achieve adhesion in the fast fluid flow of blood vessels [73]. These leuko-polymersomes achieved specific adhesion at hydrodynamic flow rates at which leukocytes adhere.…”

Designing communicating colonies of biomimetic microcapsules

“…The shells of these microcarriers are sufficiently robust to act as a protective barrier, and adequately permeable for the controlled exchange of reagents with an external solution (22). Furthermore, the permselectivity of the shells can be readily tuned (20,21,(23)(24)(25). By functionalizing the shell's outer surface, these microcarriers can bind to an underlying substrate (20).…”

“…In the ensuing discussion, we envision these synthetic systems to be polymeric microcapsules synthesized via the layer-by-layer (LbL) approach (16)(17)(18) or "polymersomes" (19)(20)(21). Such objects provide ideal platforms for creating "artificial cells," which could be tailored to exhibit a range of cellular functionality (16).…”