Benzaldehyde-Functionalized Polymer Vesicles

Abstract

Polymer vesicles with diameters of ca. 100-600 nm and bearing benzaldehyde functionalities within the vesicular walls were constructed through self assembly of an amphiphilic block copolymer PEO 45 -b-PVBA 26 in water. The reactivity of the benzaldehyde functionalities was verified by crosslinking the polymersomes, and also by a one-pot crosslinking and functionalization approach to further render the vesicles fluorescent, each via reductive amination. In vitro studies found these labelled nanostructures to undergo cell association. Keywords amphiphilic block copolymers; vesicular nanostructures; reactive polymersPolymer vesicles, also known as "polymersomes", 1-6 are supramolecular assemblies of amphiphilic block copolymers 7-14 or complementary random copolymers 15 with sizes ranging from tens of nanometers to several hundreds of microns ("giant vesicles"). Similar to liposomes, polymersomes are composed of closed bilayer membranes with hollow cavities and, therefore, have tremendous potential for encapsulation and controlled delivery. [16][17][18][19][20] Moreover, their structures can be manipulated on both polymeric and supramolecular levels to afford tunability of their properties, including size control over nanoscale to microscale dimensions, 21-24 external stimulus responses, 25-32 mechanical properties, 33-35 membrane permeability, 36-39 and in vivo fate. 40, 41 Starting from the middle of the 1990s, a variety of polymer vesicles have been developed and studied as efficient and promising candidates for the delivery of both hydrophilic (encapsulated inside the hollow cavity) and hydrophobic (loaded within the bilayer membrane wall) molecules. However, most of them consisted of amphiphilic block copolymers with limited functionalities for chemical transformations after vesicle construction. While polymersome surface functionalizations have been reported through reactions with the functionalities installed at the chain ends of the hydrophilic segments, 42, 43 there are limited literature reports associated with modifications of wall domains of polymersomes. Up to date, only radical polymerization, 33, 44 photo-induced [2+2] cyclo-addition, 15, 45-47 base-catalyzed self condensation of siloxanes, 28, 48 and ring-opening of epoxides 49 have been employed to crosslink the walls of polymer vesicles. With the increasing interests in potential biomedical applications that utilize the membrane of polymersomes as a functional unit, 18, 41, 50-53 introduction of highly reactive functionalities into polymer vesicles is being explored to expand the scope of chemistries that can be incorporated within such nanostructures. Herein, we report our approach for constructing sizetunable polymersomes with benzaldehyde functionalities (a diverse electrophile that undergoes reaction under mild conditions), as well as their crosslinking and fluorophore-functionalization via reductive amination (Scheme 1). Results and Discussion Synthesis of Amphiphilic Block Copolymer PrecursorPoly(ethylene oxide)-b-poly(4-vinyl ben...

Applications of Orthogonal “Click” Chemistries in the Synthesis of Functional Soft Materials

“…This strategy of functionalizing the same unit with different groups was extended and exploited through the formation of vesicles derived from poly(ethylene glycol)- b -poly(vinylbenzaldehyde) that were subjected to sequential reactions to attach hydrazine-functional fluorescein dyes followed by crosslinking of the nanostructure with a low molecular weight diamine. 132 Sodium cyanoborohydride was used to reduce the resulting imine and hydrazone moieties. The one-pot reaction was effective in this case, due to the fact that the hydride reagent countered the reversibility in the reactions.…”

Synthesis and Crosslinking of L‐DOPA Containing Polypeptide Vesicles

“…[3] Since most physical self-assemblies based on hydrophobic associations in water are not robust enough to survive drying or addition of organic solvents, we decided to explore the covalent crosslinking of our block copolypeptide vesicles. This strategy has been utilized successfully by other groups as a means to substantially improve vesicle stability, [2][3][4][5][6][7] but has not yet been applied to polypeptide systems.…”

“…[3][4][5][6][7] In addition to stabilizing membranes against rupture, vesicle cross-linking has also been shown to provide improved loading of cargos as well as influence their cell-binding properties. [5] The preparation of vesicles composed entirely of amino acids has been shown by ours and other groups; [8][9][10] however the covalent crosslinking of polypeptide vesicles has not been reported. Here we describe the incorporation of oxidatively crosslinkable amino acid residues into hydrophobic a-helical segments of rod-coil diblock copolypeptides and evaluate their ability to form and stabilize vesicle assemblies.…”

Stimuli-Responsive Polymersomes

“…Their membrane properties can be extensively tailored by variation of chemical structures of each polymer component (Napoli et al 2006;Mabrouk et al 2009b;Battaglia and Ryan 2005). Targeted transport can be achieved by taking advantage of the many possibilities to end-functionalize the copolymers (Lin et al 2004;Meng et al 2005;Broz et al 2005;Ben-Haim et al 2008;Christian et al 2007;Hammer et al 2008;Zupancich et al 2009;Robbins et al 2010;Nehring et al 2009;Geng et al 2006;Demirgoz et al 2009;van Dongen et al 2008;Opsteen et al 2007;Sun et al 2009). The controlled release of therapeutic substances can be integrated through the use of copolymers with blocks that respond to external or internal stimuli in the treated disease sites (Meng et al 2009;Li and Keller 2009;Du and O'Reilly 2009;Onaca et al 2009).…”