Vesicles DOI: 10.1002/anie.200801098 Sweet Talking Double Hydrophilic Block Copolymer Vesicles** George Pasparakis and Cameron Alexander* The language of cellular interactions in nature includes a wealth of code based on sugar molecules and macromolecular frameworks. [1,2] The complexity in carbohydrate structure is matched by a subtlety in function that leads to a huge variety of roles for these polymeric sugars in biology. [3,4] It is not surprising therefore that chemists seek to “talk” to biological entities through the language of the glycocode, for this would enable intervention in events such as cell-surface recognition, detection, and signaling, leading in turn to prevention of infectivity, [5] treatment of disease, [6] and even to control of new tissue formation. [7] As our comprehension of the glycocode advances, the use of synthetic sugar-containing polymers to address cells is becoming an area rich with potential. [8–13] Herein we describe an approach towards controlling cell-surface interactions and molecular transport at biointerfaces, by using self-assembling polymer vesicles with multiple copies of a simple glycoligand, glucose, as a first step towards a “conversation” between artificial cell mimics and real cells. [14] The key to this approach is the preparation of synthetic polymers capable of assembling into capsule-like structures with sugar functionality presented into solution. The aim is to produce a simple mimic of eukaryotic cell surfaces, which might in turn be recognized by biological species that normally bind to glycosylated residues on the cell. [15] To do this, we prepared block copolymers with highly hydrophilic poly(2-glucosyloxyethyl methacrylate) (pGEMA) as one block and more sparingly water-soluble poly(diethyleneglycol methacrylate) (pDEGMA) as the second block by using controlled free-radical techniques (Scheme 1 and Table 1). We chose glucose as the recognition element, as it exhibits generally weak individual interactions with receptors, but when multiple copies are present on a polymer backbone strong binding can occur through polyvalency. [16] Initial polymer synthesis involved growing a protected precursor polymer [17] by atom transfer radical polymerization (ATRP) or reversible addition–fragmentation chain transfer (RAFT) which was subsequently deprotected to render the block active and hydrophilic. This polymer was used as a macro- initiator to grow the pDEGMA block. Dynamic light scattering (DLS) showed that below 15 8C, the polymers existed in solution as separate chains, but, at 20 8C, P1 and P2 assembled into vesicles with mean diameters Scheme 1. Synthesis of glycopolymers P1 and P2. Table 1: Properties of polymers. Polymer M n [kDa] [a] M w /M n [b] x :y ratio [b] LCST [8C] [c] P1 11.2 1.34 10:50 28 P2 15.2 1.11 28:36 28 [a] Measured by gel permeation chromatography. [b] Measured by NMR spectroscopy. [c] LCST = lower critical solution temperature. [*] G. Pasparakis, Dr. C. Alexander School of Pharmacy, University of Nottingham Nottingham, NG7 2RD (UK) Fax: (+ 44)115-951-5102 E-mail: cameron.alexander@nottingham.ac.uk [**] This work was supported by the Engineering and Physical Sciences Research Council (Grant EP). We also thank Dr. Kris Thurecht for RAFT agents, Dr. Natalio Krasnogor and Prof. Steve Howdle for helpful discussions, and Dr. Alan Cockayne for help with micro- biological assays and analysis. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie 4847 Angew. Chem. Int. Ed. 2008, 47, 4847 –4850 # 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim