Nanogel Star Polymer Nanostructures of Controlled Size, Molecular Architecture and Functionality: No Assembly Required R.D. Miller,  J. Sly  , V. Y. Lee 1 , E. Appel  , , M. Tijo 1 , T. Nguyen 2 , H. Nunes 2 L. Gomez 2 , M. McNeil 2 , J. Munninghoff 3 , A.E. Rowan 3 1 IBM Almaden Research Center 650 Harry Rd, San Jose CA 95120; 408-927-1646; F 408-927-3310; rdmiller@almaden.ibm.com 2 San Jose State University One Washington Square, San Jose CA 95192; 3 Radboud University Nijmegen, Nijmegen, The Netherlands ABSTRACT We have developed versatile routes to nanogel core, multiarm stars and polymeric unimolecular amphiphiles that provide exquisite control over molecular size, polydispersity, chain and peripheral functionality etc. The number of arms is adjustable from 20 to more than 100. The synthetic route is cheap and scalable and purification is simple providing an intrinsic advantage over dendrimers. These materials readily encapsulate a variety of hydrophobic materials at reasonable loading levels (10- 15%) without covalent binding. The cores and arms can be bio- stable, -degradable or –compatible. In addition to small molecules, nanoparticles including superparamagnetic materials can be encapsulated in the outer shell through ligand-mediated binding. The outer shell and periphery can also catalyze the controlled deposition of various inorganic shells including organosilicates and gold. The nanoparticles are multicompartmental and are useful as dual function reagents for therapeutics and imaging. Keywords: nanogel stars, synthesis, characterization, encapsulation Introduction: Micellar nanostructures produced by the self assembly of block copolymers have been widely studied for the encapsulation of small molecules including drugs and therapeutic reagents [1]. These structures improve reagent solubility and provide a level of protection toward degradation under physiological conditions. The micellar structures are, however, dynamic assemblies which are easily destroyed. We are studying soft colloid, multiarm star polymers where the polymer arms emanate from a nanogel core (Figure 1). The topology of such nanogel star polymer materials can be similar to dendrimers providing a central core region, various molecular compartments for encapsulation and a plethora of functionality which can be distributed throughout the polymer arms and/or localized on the periphery [2]. These materials are easier and cheaper to synthesize on a large scale, simpler to purify and offer more functional variety and distribution than dendrimers. There are four main techniques that have been discussed for the preparation of star polymers using controlled polymerization techniques: (i) arm first/static core [3] (ii) core first/static core [4] (iii)core first/living core [5] and (iv) arm first/living core [6]. Polymer control has been achieved using anionic, controlled free radical, cationic and ring opening polymerization (ROP) techniques. In this discussion, we have focused on nanogel star polymers produced by the arm first/living core route utilizing both anionic and ring opening polymerization with organic catalysts (OROP) [7] to generate both the initial arms and the crosslinked core. Unimolecular amphiphiles are generated by postpolymerization transformation. Discussion: Recently we have described the preparation of nanogel star polymer utilizing anionic techniques to form the core and the initial arms [2]. The use of functionalized initiators allows the decoration of the polymers formed with other small molecules or polymers. When the peripherial functionality is converted to an initiator, polymeric arms can be grown fron the nanogel star using controlled radical polymerization usually atom transfer radical polymerization [8] to produce block copolymer arms. Alternatively, preformed polymers (e.g. PEG) can be appended through postpolymerization coupling to generate block copolymer arms. Anionic polymerization is usually initiated using styrene monomer at room temperature in cyclohexane and the core is generated with divinylbenzene as the crosslinking core forming reagent. In our hands, purified p- divinylbenzene yields the best and most dependable results. Polydispersities of the functionalized nanogel stars prepared using this process are typically in the 1.1-1.25 range. By varying the stoichiometry of the reagents , we can control the molecular size and number of arms in the initial star nanogel polymer. By using an anionic initiator such as 3- tert-butyldimethylsiloxy propyl lithium, hydroxyl functionality is installed at the ends of the star polymer chain. This permits further functionalization after the formation of the initial star polymer core (vide infra). The arms emanating from the nanogellated core can be homo or block copolymers which are prepared as a first step by anionic [6], controlled radical [9], cationic [10] or ring opening polymerization [11] and subsequently used to create the microgel core. For ROP, we have used organic catalysts (OROP) rather than the more traditional metallic catalysts. For the controlled ring opening of lactones such as valero- and capro-lactone, we have most often used 1,5,7-triaza-bicyclo[4.4.0]dec-5-ene (TBD) as the catalyst and an alcohol initiator (Scheme I). As a crosslinking NSTI-Nanotech 2012, www.nsti.org, ISBN 978-1-4665-6274-5 Vol. 1, 2012 464