Formation and characterization of polyglutamate core-shell microspheres

The need for organ-targeted delivery of drugs and imaging agents creates an interest in biocompatible, biodegradable vesicles. We make protein microspheres using high-intensity ultrasound; these microspheres have a protein shell and a hydrophobic interior, making them ideal for delivering hydrophobic materials. We have previously shown that various proteins, e.g., bovine serum albumin (BSA), form a microsphere shell stabilized by interprotein cross-linking of cysteine residues. In this study, polyglutamate was used to form core-shell microspheres at slightly basic pH using sonication. These particles are smaller than our previous protein microspheres and are stable under conditions encountered in vivo. The stability of polyglutamate microspheres appears to be due to hydrogen bonding networks and not covalent cross-linking.     

Engineered microsphere contrast agents for optical coherence tomography

Contrast agents are utilized in virtually every imaging modality to enhance diagnostic capabilities. We introduce a novel class of optical contrast agent, namely, encapsulating microspheres, that are based not on fluorescence but on scattering nanoparticles within the shell or core. The agents are suitable for reflection- or scattering-based techniques such as optical coherence tomography, light microscopy, and reflectance confocal microscopy. We characterize the optical properties of gold-, melanin-, and carbon-shelled contrast agents and demonstrate enhancement of optical coherence tomography imaging after intravenous injection of such an agent into a mouse.     

Tumor targeting by surface-modified protein microspheres

Protein microspheres have been used in the fields of biomedical imaging and drug delivery, but surface modification for cell targeting has been problematic. We have for the first time used an electrostatic adhesion approach to adhere arginine-glutamic acid-aspartic acid (RGD) containing peptides to the surface of protein microspheres for the purpose of targeting these vesicles to tumor cells. RGD sequences are recognized by integrin membrane receptors, which are overexpressed in various tumors. We have succeeded in modifying the surface of serum albumin core-shell microspheres, which have a fluorescent nonaqueous core by using several polylysine peptides containing the RGD sequence. Fluorescence microscopy reveals that these modified microspheres are selectively bound and taken up by HT29 human colon cancer cells in vitro.     

The spectral density of the QCD Dirac operator and patterns of chiral symmetry breaking

We study the spectrum of the QCD Dirac operator for two colors with fermions in the fundamental representation and for two or more colors with adjoint fermions. For N_f flavors, the chiral flavor symmetry of these theories is spontaneously broken according to SU (2N_f → Sp (2N_f) and SU (N_f → O (N_f), respectively, rather than the symmetry breaking pattern SU (N_f) × SU (N_f) → SU (N_f) for QCD with three or more colors and fundamental fermions. In this paper we study the Dirac spectrum for the first two symmetry breaking patterns. Following previous work for the third case we find the Dirac spectrum in the domain λ Λ_QCD by means of partially quenched chiral perturbation theory. In particular, this result allows us to calculate the slope of the Dirac spectrum at λ = 0. We also show that for λ 1/L₂ Λ_QCD (wing L the linear size fo the system) the Dirac spectrum is given by a chiral Random Matrix Theory with the symmetries of the Dirac operator.