Glaucoma is the leading irreversible cause of blindness in the world. We are developing a new image-guidance system to deliver a neuroprotective drug in a controlled release nanosponge. The system consists of a magnetically tracked image-guidance system, the nanosponge material and the drug. We have characterized the performance of each aspect in phantoms, animals and ex-vivo human tissue.

AIMS:Antibodies are the principal mediator of immunity against reinfection with viruses. Antibodies typically neutralize viruses by binding to virion particles in solution prior to attachment to susceptible cells. Once viruses enter cells, conventional antibodies cannot inhibit virus infection or replication. It is desirable to develop an efficient and nontoxic method for the introduction of virus-inhibiting antibodies into cells.MATERIALS & METHODS:In this article, we report a new method for the delivery of small recombinant antibody fragments into virus-infected cells using a dendrimer-based molecular transporter.RESULTS & CONCLUSION:The construct penetrated virus-infected cells efficiently and inhibited virus replication. This method provides a novel approach for the immediate delivery of inhibitory antibodies directed to virus proteins that are exposed only in the intracellular environment. This approach circumvents the current and rather complicated expression of inhibitory antibodies in cells following gene transfer.

Introduction: Targeting of cancer by chemotherapy in combination with anti-vascular endothelial growth factor (VEGF) therapy has demonstrated not only the clinical efficacy but also a higher risk of serious hematologic complications including neutropenia The purpose of the study was to elucidate the molecular mechanisms responsible for the development of neutropenia during the combination treatmentMethods: Mouse model and in vitro studies were undertaken to determine the effect of Interference with VEGF signaling by VEGF-specific agents or a multitargeted VEGF receptor (VEGFR) tyrosine kinase inhibitor on proliferation of hematopoietic progenitor cell (HPC) and repopulation of the hematopoietic compartment after myeloablationResults: The studies demonstrated that blockage of VEGFR1 or VEGFR2 signaling decreased HPC proliferation and impaired repopulation of the hematopoietic compartment after myelosuppression by slowing the progression of HPC through the cell cycle The combination of cytotoxic drugs and VEGFR tyrosine kinase inhibitor had an additive inhibitory effect and decreased proliferation of HPC significantly stronger than either agent aloneConclusions: Signaling through both VEGFR1 and VEGFR2 is required for normal reconstitution of the hematopoietic compartment after cytotoxic chemotherapy

Structurally robust block copolymer templates with feature sizes of approximately 10 nm were prepared from functionalized poly(methyl methacrylate)-b-polystyrene block copolymers. By the inclusion of benzoeyclobutene crosslinking groups in the polystyrene block, the covalent stabilization of thin films to both thermal treatment and solvent exposure became possible. In addition, the crosslinking of the poly(styrene-benzoeyclobutene) domains at 220 degreesC, followed by the removal of poly(methyl methaerylate), provided a robust, crosslinked nanostructure with greater processing and fabrication potential. (C) 2005 Wiley Periodicals, Inc.

A novel approach is presented for the controlled intramolecular collapse of linear polymer chains to give well-defined single-molecule nanoparticles whose structure is directly related to the original linear polymer. By employing a combination of living free radical polymerization and benzocyclobutene (BCB) chemistry, nanoparticles can be routinely prepared in multigram quantities with the size being accurately controlled by either the initial degree of polymerization of the linear chain or the level of incorporation of the BCB coupling groups. The latter also allows the cross-link density of the final nanoparticles to be manipulated. In analogy with dendritic macromolecules, a significant reduction of up to 75% in the hydrodynamic volume is observed on going from the starting random coil linear chains to the corresponding nanoparticles. The facile nature of the living free radical process also permits wide variation in monomer selection and functional group incorporation and allows novel macromolecular architectures to be prepared. Furthermore, the use of block copolymers functionalized with benzocyclobutene groups in only one of the blocks gives, after intramolecular collapse, a hybrid architecture in which a single linear polymer chain is attached to the globular nanoparticle.

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Surface-initiated living free-radical polymerization is employed in a multistep procedure to prepare hollow polymeric nanocapsules. Initially, trichlorosilyl-substituted alkoxyamine initiating groups are attached to the surface silanol groups of silica nanoparticles. This surface layer of initiating groups is then used to grow functionalized linear chains leading to a core-shell morphology. The choice of functional groups is governed by their ability to undergo facile crosslinking reactions, with both active ester and benzocyclobutene groups being examined. Under either chemical or thermal conditions, the reaction of these functionalities gives a crosslinked polymeric shell that is covalently attached to, and surrounds, the central silica core. Removal of the silica core with HF then gives the hollow polymeric nanocapsules, which are stable under solvent dissolution and thermal treatment because of their crosslinked structure. (C) 2002 Wiley Periodicals, Inc.

A recent approach taken to create organic nanoparticles involves the self-crosslinking of a single polymer chain. This process is highly dependent on the latent crosslinking chemistry and density, as well as the polymer type, functionality, and architecture. In order to more accurately study the affects of the shape and size of specific nanoparticles, a caprolactone with a ferrocene functional group can be introduced in a cross-linkable caprolactone-copolymer. The iron atom present in these nanoparticles allows for a visible representation of the nanoparticles in a Transmission Electron Microscope (TEM). Therefore, functionalized caprolactone monomers were synthesized in multistep procedures, utilizing, among others, the Mitsunobu Reaction to add functional groups to the caprolactone ring via an ester bond.

The influence of macromolecular architecture on the physical properties of polymeric materials has been studied by comparing poly(benzyl ether) dendrons with their exact linear analogues. The results clearly confirm the anticipation that dendrimers are unique when compared to other architectures. Physical properties, from hydrodynamic volume to crystallinity, were shown to be different, and in a comparative study of core encapsulation in macromolecules of different architecture, energy transduction from the polymer backbone to a porphyrin core was shown to be different for dendrimers as compared to that of isomeric four- or eight-arm star polymers. Fluorescence excitation revealed strong, morphology dependent intramolecular energy transfer in the three macromolecular isomers investigated. Even at high generations, the dendrimers exhibited the most efficient energy transfer, thereby indicating that the dendritic architecture affords superior site isolation to the central porphyrin it surrounds.

The nitroxide-mediated living free-radical polymerization of 1,2,5,6-di(isopropylidene)-D-glucose-2-propenoate was achieved in dimethylformamide at 105 degreesC with an alpha-hydrido alkoxyamine initiator functionalized with a lipophilic N,N-di(octadecyl)amine group, The kinetics of the polymerization were investigated, and the mechanism was shown to be a living process allowing, after hydrolysis, controlled molecular weight, low-polydispersity lipo-glycopolymers to be prepared. The amphiphilic character of the macromolecule could be altered by either the exchange of the alkoxyamine at the chain end with hydrogen or the preparation of copolymers with lipophilic monomers such as N,N-di(octadecyl)acrylamide. The surface and membrane-forming properties of these novel lipopolymers demonstrate their amphiphilic character. (C) 2002 Wiley Periodicals, Inc.

Intramolecular H-bonding has been shown to be a powerful tool in increasing the performance of alkoxyamine initiators for nitroxide mediated living free radical polymerizations.

A novel method for the functionalization of vinyl polymers prepared by nitroxide-mediated living free radical procedures is reported. This strategy is based on the controlled monoaddition of maleic anhydride and maleimide derivatives to the alkoxyamine chain end followed by elimination of the mediating nitroxide radical. This allows the introduction of a wide variety of functional groups with high efficiency, while at the same time permitting the alkoxyamine functional group to be removed and the thermal stability of the polymer chain to be increased.