No abstract

S emiconductor nanocrystals, also known as quantum dots (QDs), have emerged as a significant new class of materials over the past decade. The ability to synthesize highly monodisperse colloidal QDs, has paved the way for numerous spectroscopic studies assigning the QD electronic states and mapping out their evolution as function of size. 1,2 Fundamental understanding of these semiconductor nanocrystals has further stimulated the development of new materials, such as quantum nanorods, 3 magnetic nanocrystals, 4 QD-based solar cells, and light-emitting devices. 5 These related materials augment the large potential for using luminescent QDs as labeling reagents to empower numerous biotechnological applications.The unique optical and spectroscopic properties of QDs offer a compelling alternative to traditional fluorophores in almost all fluorescence-based applications. 6 The radii of QDs are smaller than the average physical separation between the electrons and holes (Exciton Bohr Radius), which results in a class of materials that dwell between the molecular and bulk forms of matter. Quantum confinement of both the electron and hole in all three dimensions leads to quantized energy levels or band gaps, which increase with decreasing crystal- ABSTRACT:Nanocrystalline semi-conductor materials, called quantum dots (QDs), exhibit unique optical and spectroscopic properties, which include broad absorption,

We report a robust and practical method for the preparation of water-soluble luminescent quantum dots (QDs) selectively coupled through an amine or thiol linkage to peptide ligands targeted to G-protein coupling receptors (GPCRs) and demonstrate their utility in whole-cell and single-molecule imaging. We utilized a low molecular weight ( approximately 1200 Da) diblock copolymer with acrylic acids as hydrophilic segments and amido-octyl side chains as hydrophobic segments for facile encapsulation of QDs (QD 595 and QD 514) in aqueous solutions. As proof of principle, these QDs were targeted to the human melanocortin receptor (hMCR) by chemoselectively coupling the polymer-coated QDs to either a hexapeptide analog of alpha-melanocyte stimulating hormone or to the highly potent MT-II ligand containing a unique amine. To label QDs with ligands lacking orthogonal amines, the diblock copolymers were readily modified with water-soluble trioxa-tridecanediamine to incorporate freely available amine functionalities. The amine-functionalized QDs underwent facile reaction with the bifunctional linker NHS-maleimide, allowing for covalent coupling to GPCR-targeted ligands modified with unique cysteines. We demonstrate the utility of these maleimide-functionalized QDs by covalent conjugation to a highly potent Deltorphin-II analog that allowed for selective cell-surface and single-molecule imaging of the human delta-opioid receptor (hDOR).

We describe a new family of discrete supramolecules comprising leucine-zipper peptides noncovalently assembled upon cognate leucine zippers fused to a dendrimer core. Circular dichroism and sedimentation equilibrium experiments clearly demonstrate that each leucine-zipper dendrimer (D-EZ4 or D-KZ4) can noncovalently display four leucine zippers on their surface that can be utilized for the multivalent display of protein cargo. Furthermore, we show that matched leucine-zipper dendrimers (D-EZ4/D-KZ4) can self-organize into fibers at neutral pH, providing a new scaffold for nanotechnology.

BackgroundRecent studies have shown that androgen displays an inhibitory effect on breast cancer cell lines that express androgen receptor (AR) but not estrogen receptor (ER) and progesterone receptor (PR). We have previously reported that approximately 1/3 of ER negative high grade invasive ductal carcinomas express AR. Thus, AR can serve as a potential therapeutic target for this group of patients.AimHere we investigated AR expression patterns in 980 consecutive breast carcinomas.ResultsWe found that (1) AR was expressed more frequently (77%) than ER (61%) and PR (60%) in breast carcinomas; (2) AR expression was associated with ER and PR expression (P < 0.0001), small tumor size (P = 0.0324) and lower Ki-67 expression (P = 0.0013); (3) AR expression was found in 65% of ER negative tumors; (4) AR expression was associated with PR and Ki-67 in ER negative tumors, but not in ER positive tumors; (5) AR expression was higher in ER positive subtypes (Luminal A, Luminal B and Luminal HER2 subtypes, 80%–86%) and lower in ER negative subtypes [HER2, triple negative (TN), and TN EFGR positive subtypes; 52%–66%], with over 50% of TN tumors expressing AR.ConclusionMore breast carcinomas express AR than ER and PR, including significant numbers of ER negative and TN tumors, for which AR could serve as a potential therapeutic target.