Synthesis and characterization of core-shell star copolymers for in vivo PET imaging applications.

The synthesis of core-shell star copolymers via living free radical polymerization provides a convenient route to three-dimensional nanostructures having a poly(ethylene glycol) outer shell, a hydrophilic inner shell bearing reactive functional groups, and a central hydrophobic core. By starting with well-defined linear diblock copolymers, the thickness of each layer, overall size/molecular weight, and the number of internal reactive functional groups can be controlled accurately, permitting detailed structure/performance information to be obtained. Functionalization of these polymeric nanoparticles with a DOTA-ligand capable of chelating radioactive (64)Cu nuclei enabled the biodistribution and in vivo positron emission tomography (PET) imaging of these materials to be studied and correlated directly to the initial structure. Results indicate that nanoparticles with increasing PEG shell thickness show increased blood circulation and low accumulation in excretory organs, suggesting application as in vivo carriers for imaging, targeting, and therapeutic groups.

A templating approach for monodisperse self-assembled organic nanostructures.

The precise structural control is known for self-assembly into closed spherical structures (e.g., micelles), but similar control of open structures is much more challenging. Inspired by natural tobacco mosaic virus, we present the use of a rigid-rod template to control the size of a one-dimensional self-assembly. We believe that this strategy is novel for organic self-assembly and should provide a general approach to controlling size and dimension.

Structural effects on the biodistribution and positron emission tomography (PET) imaging of well-defined (64)Cu-labeled nanoparticles comprised of amphiphilic block graft copolymers.

The synthesis of poly(methyl methacrylate-co-methacryloxysuccinimide-graft-poly(ethylene glycol)) (PMMA-co-PMASI-g-PEG) via living free radical polymerization provides a convenient route to well-defined amphiphilic graft copolymers having a controllable number of reactive functional groups, variable length PEG grafts, and low polydispersity. These copolymers were shown to form PMMA-core/PEG-shell nanoparticles upon hydrophobic collapse in water, with the hydrodynamic size being defined by the molecular weight of the backbone and the PEG grafts. Functionalization of these polymeric nanoparticles with a 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) ligand capable of chelating radioactive 64Cu nuclei enabled the biodistribution and in vivo positron emission tomography of these materials to be studied and directly correlated to the initial structure. Results indicate that nanoparticles with increasing PEG chain lengths show increased blood circulation and low accumulation in excretory organs, suggesting the possible use of these materials as stealth carriers for medical imaging and systemic administration.

Labeling of Polymer Nanostructures for Medical Imaging: Importance of crosslinking extent, spacer length, and charge density.

Radiolabeling studies were employed to investigate the influence of structure on the efficiency of surface functionalization for poly(acrylic acid)-coated shell crosslinked nanoparticles (SCKs) with two types of amine-terminated DOTA chelators. An intricate interplay between the chemical and physical properties of both the DOTA derivative and the SCK nanostructures was revealed, demonstrating the importance of structural control.

Mirror image nanostructures.

Chiral molecules that self-assemble to form chiral supramolecular structures exhibit interesting structural features reminiscent of tertiary and quaternary structures of proteins and have applications in catalysis and nonlinear optics. Often, these structures are hierarchical, with their chiral structure difficult to interpret on the molecular scale. In this communication, we observe chiral assembling molecules that form well-defined helices with a pitch of 28 nm. We observe the behavior in both R- and S-enantiomers of the molecule, forming mirror image nanostructures. The molecular chirality is determined by the dimethyloctyl alkyl coil of the molecule and is located more than 4 nm from the hydrogen-bonding segment. The nanostructures observed are not hierarchical, which could be a result of the significant separation between the stereocenter and hydrogen-bonding dendron. The subtle structural modification at the periphery of the molecule biases the supramolecular assembly, which is driven primarily by strong hydrogen-bonding and pi-pi stacking interactions.

Synthesis, self-assembly, and characterization of supramolecular polymers from electroactive dendron rodcoil molecules.

We report here the synthesis and self-assembly of a series of three molecules with dendron rodcoil architecture that contain conjugated segments of oligo(thiophene), oligo(phenylene-vinylene), and oligo(phenylene). Despite their structural differences, all three molecules yield similar self-assembled structures. Electron and atomic force microscopy reveals the self-assembly of the molecules into high aspect ratio ribbon-like nanostructures which at low concentrations induce gelation in nonpolar solvent. Self-assembly results in a blue-shifted absorption spectrum and a red-shifted, quenched fluorescence spectrum, indicating aggregation of the conjugated segments within the ribbon-like structures. The assembly of these molecules into one-dimensional nanostructures is a route to pi-pi stacked supramolecular polymers for organic electronic functions. In the oligo(thiophene) derivative, self-assembly leads to a 3 orders of magnitude increase in the conductivity of iodine-doped films due to self-assembly. We also found that electric field alignment of these supramolecular assemblies can be used to create arrays of self-assembled nanowires on a device substrate.