Quantum dot-polymer nanocomposites : new materials for dispersion, encapsulation, and electronic applications.

Tremendous advances in the synthesis and functionalization of nanoparticles over the past twenty years have resulted in remarkable discoveries in the field of nanotechnology. One such development is found in quantum dots, semiconductor nanoparticles that exhibit unique optical and electronic properties not found in the bulk. Research efforts associated with the combination of quantum dots and polymers center on uniting the mechanical or processing properties of the polymer with the optical properties of the quantum dot. Simply blending polymers with nanoparticles typically leads to nanoparticle aggregation, which negates the inherent advantageous properties of the quantum dots. The development of organic and polymer ligands for nanoparticle surface modification enables the preparation of dispersed nanocomposites that retain, or even enhance, the original nanoparticle properties. Presented here is the synthesis of functionalized nanoparticles that are tailored for the growth of polymers directly from the particle surface. Initial studies focused on the preparation of nanoparticle-polymer hybrid materials where the nanoparticles were evenly dispersed throughout the polymer. A method was developed to cross-link polymers grafted from the nanoparticle in an encapsulating shell, with the goal of minimizing nanoparticle degradation. In addition, polymerization chemistry from quantum dot surfaces was modified and optimized to produce conjugated polymer-quantum dot composites. The coupling of these two electronically active components gave composite materials with very unique optical properties that hold potential as displays, sensors, and light-emitting materials

A Versatile Polymer Micelle Drug Delivery System for Encapsulation and In Vivo Stabilization of Hydrophobic Anticancer Drugs

Chemotherapeutic drugs are widely used for the treatment of cancer; however, use of these drugs is often associated with patient toxicity and poor tumor delivery. Micellar drug carriers offer a promising approach for formulating and achieving improved delivery of hydrophobic chemotherapeutic drugs; however, conventional micelles do not have long-term stability in complex biological environments such as plasma. To address this problem, a novel triblock copolymer has been developed to encapsulate several different hydrophobic drugs into stable polymer micelles. These micelles have been engineered to be stable at low concentrations even in complex biological fluids, and to release cargo in response to low pH environments, such as in the tumor microenvironment or in tumor cell endosomes. The particle sizes of drugs encapsulated ranged between 30–80 nm, with no relationship to the hydrophobicity of the drug. Stabilization of the micelles below the critical micelle concentration was demonstrated using a pH-reversible crosslinking mechanism, with proof-of-concept demonstrated in both in vitro and in vivo models. Described herein is polymer micelle drug delivery system that enables encapsulation and stabilization of a wide variety of chemotherapeutic drugs in a single platform

IT-141, a Polymer Micelle Encapsulating SN-38, Induces Tumor Regression in Multiple Colorectal Cancer Models

Polymer micelles are promising drug delivery vehicles for the delivery of anticancer agents to tumors. Often, anticancer drugs display potent cytotoxic effects towards cancer cells but are too hydrophobic to be administered in the clinic as a free drug. To address this problem, a polymer micelle was designed using a triblock copolymer (ITP-101) that enables hydrophobic drugs to be encapsulated. An SN-38 encapsulated micelle, IT-141, was prepared that exhibited potent in vitro cytotoxicity against a wide array of cancer cell lines. In a mouse model, pharmacokinetic analysis revealed that IT-141 had a much longer circulation time, plasma exposure, and tumor exposure compared to irinotecan. IT-141 was also superior to irinotecan in terms of antitumor activity, exhibiting greater tumor inhibition in HT-29 and HCT116 colorectal cancer xenograft models at half the dose of irinotecan. The antitumor effect of IT-141 was dose-dependent and caused complete growth inhibition and tumor regression at well-tolerated doses. Varying the specific concentration of SN-38 within the IT-141 micelle had no detectible effect on this antitumor activity, indicating no differences in activity between different IT-141 formulations. In summary, IT-141 is a potent micelle-based chemotherapy that holds promise for the treatment of colorectal cancer

Track Extrapolation and Distribution for the CDF-II Trigger System

The CDF-II experiment is a multipurpose detector designed to study a wide range of processes observed in the high energy proton-antiproton collisions produced by the Fermilab Tevatron. With event rates greater than 1MHz, the CDF-II trigger system is crucial for selecting interesting events for subsequent analysis. This document provides an overview of the Track Extrapolation System (XTRP), a component of the CDF-II trigger system. The XTRP is a fully digital system that is utilized in the track-based selection of high momentum lepton and heavy flavor signatures. The design of the XTRP system includes five different custom boards utilizing discrete and FPGA technology residing in a single VME crate. We describe the design, construction, commissioning and operation of this system.Comment: 34 pages, 9 figures, submitted to Nucl.Inst.Meth.

Melanocortin 1 receptor ligands and methods of use

The subject invention pertains to a modified MC1R peptide ligand comprising a peptide that is a melanocortin 1 receptor (MC1R) ligand and a functionality or linker, such as a click functionality, for conjugation to a surface or agent. The modified MC1R peptide ligand can be coupled, e.g., via a click reaction with a complementary click functionality attached, to a moiety to form an MC1R-targeted agent. Drugs, contrast agents, polymers, particles, micelles, surfaces of larger structures, or other moieties can be targeted to the MC1R. The subject invention also pertains to a MC1R peptide ligand-micelle complex comprising a peptide that is a melanocortin 1 receptor ligand connected via a click reaction product to a micelle. The micelle is stable in vivo and can target melanoma tumor cells by association of the peptide ligand with the MC1R or the tumor and selectively provide a detectable and/or therapeutic agent (such as an imageable contrast agent and/or anti-cancer agent) selectively to the tumor cell.Board of Regents, University of Texas Syste

Stabilized Polymer Micelles for the Development of IT-147, an Epothilone D Drug-Loaded Formulation

Epothilones have demonstrated promising potential for oncology applications but suffer from a narrow therapeutic window. Epothilone D stabilizes microtubules leading to apoptosis, is active against multidrug-resistant cells, and is efficacious in animal tumor models despite lack of stability in rodent plasma. Clinical development was terminated in phase II due to dose limiting toxicities near the efficacious dose. Taken together, this made epothilone D attractive for encapsulation in a stabilized polymer micelle for improved safety and efficacy. We have designed a library of triblock copolymers to develop IT-147, a lead formulation of epothilone D that extends plasma circulation for accumulation in the tumor environment, and potentially decrease systemic exposure to reduce dose limiting toxicities. The drug loading efficiency for IT-147 exceeds 90%, is 75 nm in diameter, and demonstrates pH-dependent release of epothilone D without chemical conjugation or enzymatic activation. Administration of IT-147 at 20 mg/kg increases exposure of epothilone D to the plasma compartment over 6-fold compared to free drug. At the same dose, 20 mg/kg epothilone D from IT-147 is considered the no observed adverse effect level (NOAEL) but is the maximum tolerated dose for free drug. Consequently, IT-147 is positioned to be a safer, more effective means to deliver epothilone D

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació