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To expand the single-dose duration over which noninvasive clinical and preclinical cancer imaging can be conducted with high sensitivity, and well-defined spatial and temporal resolutions, a facile strategy to prepare ultrasmall nanoparticulate X-ray contrast media (nano-XRCM) as dual-modality imaging agents for positron emission tomography (PET) and computed tomography (CT) has been established. Synthesized from controlled copolymerization of triiodobenzoyl ethyl acrylate and oligo(ethylene oxide) acrylate monomers, the amphiphilic statistical iodocopolymers (ICPs) could directly dissolve in water to afford thermodynamically stable solutions with high aqueous iodine concentrations (>140 mg iodine/mL water) and comparable viscosities to conventional small molecule XRCM. The formation of ultrasmall iodinated nanoparticles with hydrodynamic diameters of ca. 10 nm in water was confirmed by dynamic and static light scattering techniques. In a breast cancer mouse model, in vivo biodistribution studies revealed that the 64Cu-chelator-functionalized iodinated nano-XRCM exhibited extended blood residency and higher tumor accumulation compared to typical small molecule imaging agents. PET/CT imaging of tumor over 3 days showed good correlation between PET and CT signals, while CT imaging allowed continuous observation of tumor retention even after 10 days post-injection, enabling longitudinal monitoring of tumor retention for imaging or potentially therapeutic effect after a single administration of nano-XRCM.

The construction of nanostructures from biodegradable precursors and shell/core crosslinking have been pursued as strategies to solve the problems of toxicity and limited stability, respectively. Polyphosphoester (PPE)-based micelles and crosslinked nanoparticles with non-ionic, anionic, cationic, and zwitterionic surface characteristics for potential packaging and delivery of therapeutic and diagnostic agents, were constructed using a quick and efficient synthetic strategy, and importantly, demonstrated remarkable differences in terms of cytotoxicity, immunotoxicity, and biofouling properties, as a function of their surface characteristics and also with dependence on crosslinking throughout the shell layers. For instance, crosslinking of zwitterionic micelles significantly reduced the immunotoxicity, as evidenced from the absence of secretions of any of the 23 measured cytokines from RAW 264.7 mouse macrophages treated with the nanoparticles. The micelles and their crosslinked analogs demonstrated lower cytotoxicity than several commercially-available vehicles, and their degradation products were not cytotoxic to cells at the range of the tested concentrations. PPE-nanoparticles are expected to have broad implications in clinical nanomedicine as alternative vehicles to those involved in several of the currently available medications., National Heart, Lung, and Blood Institute (Program of Excellence in Nanotechnology HHSN268201000046C), National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (R01-DK082546), National Science Foundation (U.S.) (Grant DMR-0906815), National Science Foundation (U.S.) (Grant DMR-1105304), Robert A. Welch Foundation (W. T. Doherty-Welch Chair in Chemistry, Grant A-0001), National Institutes of Health (U.S.) (NIH P30 DC004665)

Rigid nanoscale polymer rods were prepared by grafting preformed amine-terminated poly(styrene) and poly(tert-butyl acrylate) onto oxidized cellulose microcrystals. Low polydispersity polymers, grown using atom transfer radical polymerization, were characterized and purified prior to cellulose attachment. Oxidation of the cellulose microcrystal led to the formation of carboxylic acids on the surface of the microcrystals. Covalent attachment of the polymers onto the cellulose microcrystals was achieved via a carbodiimide-mediated amidation reaction. The length and diameter of the polymer-cellulose composites increased upon surface modification. Typically, polymer-cellulose composites are synthesized by a grafting-from method because it can be difficult to obtain sufficient graft density using a grafting-to preparation. However, the composites reported here comprised 60-64% grafted polymer by mass. This degree of grafting-to allowed the composite to form stable suspensions in organic solvents., QC 20110506

Hydroxypropyl cellulose (HPC) was used as a core molecule for controlled grafting of monomers by ATRP, the aim being to produce densely grafted comb polymers. HPC was either allowed to react with an ATRP initiator or the first generation initiator-functionalized 2,2-bis(methylol)propionic acid dendron to create macroinitiators having high degrees of functionality. The macroinitiators were then "grafted from" using ATRP of methyl methacrylate (MMA) or hexadecyl methacrylate. Block copolymers were obtained by chain extending PMMA-grafted HPCs via the ATRP of tert-butyl acrylate. Subsequent selective acidolysis of the tert-butyl ester moieties was performed to form a block of poly(acrylic acid) resulting in amphiphilic block copolymer grafts. The graft copolymers were characterized by H-1 NMR and FT-IR spectroscopies, DSC, TGA, rheological measurements, DLS, and tapping mode AFM on samples spin coated upon mica. It was found that the comb (co)polymers were in the nanometer size range and that the dendronization had an interesting effect on the rheological properties., QC 20100826

The conformation of cross-linked, monomolecular, polystyrene nanoparticles on a solid substrate is considered as a function of cross-linking degree and substrate surface free energy. It is found that an extreme amount of cross-linking is necessary for the ca. 5-10 nm diameter nanoparticles to retain their original spherical shape, regardless of surface free energy. A lesser amount of cross-linking produces a nanoparticle that collapses to a pancake-like conformation on a high-energy substrate yet remains spherical on a low-energy surface. A simple model is developed to reveal the relationship between nanoparticle modulus and surface free energy to define the nanoparticle conformation., QC 20120309

Hyperbranched polymers of unique compositions were studied for their mechanical properties and degradation behaviors. Highly branched polymeric architectures have been shown to exhibit properties that are unique to those of linear polymer materials. In the studies supported under this grant, hyperbranched polycarbonates were designed as analogs to common engineering polymers to investigate the effects of branching upon the chain-chain packing and cooperative motions. Remarkably, the local chain-chain interactions were quite similar for hyperbranched and linear polymer isomers. In another design, hyperbranched poly(silyl ester)s were studied as hydrolytically-degradable polymers to determine the effects of branching upon the degradation profile. The hyperbranched poly(silyl ester)s degraded by a two step degradation profile, whereas the analogous linear polymer gave smooth molecular weight loss with time. The result of these undertakings was the preparation of new materials and the acquisition of improved understanding of the structural conformation, three-dimensional solid-state packing, and physical and mechanical properties of highly-branched polymers.

Macromolecular structures of varying architectures have been prepared and studied, in order to gain a fundamental understanding of the role of molecular parameters upon the properties of polymeric materials and to lead to the development of unique and advanced materials. Improved knowledge of the structural conformation, three-dimensional solid-state packing, and physical and mechanical properties of highly-branched polymers has been gathered through several means of investigation, each involving the study of fluorine-containing dendritic or hyperbranched polymers. Dendritic (tree-like) macromolecules have been shown by several research groups to possess very interesting behavior, due to a three-dimensional globular shape, branched architecture and large number of chain end functionalities. By placing a fluorine atom at the focal point of the globular dendritic molecule, we have quantitatively determined the intramolecular location of the chain end groups relative to the remainder of the structure as being distributed throughout the internal and external regions, and have characterized the nature of intermolecular packing in the solid state. The micromechanical properties of ultra-thin film samples of dendritic macromolecules have been measured by atomic force microscopy, and comparisons have been made with linear polymers of exact compositional equivalence. This research then inspired the study of dendritic and hyperbranched polymers, which contained a high level of fluorocarbon groups to impart low surface energies and create minimally-interacting nanoscale globular molecules. Surface energies and adhesive forces lower than those for PTFE were accomplished, and these materials showed superior performance in applications such as mold release agents.