Fluorescent Organic Nanoparticles that are Monovalent, Ultra-Stable, and Biocompa

单价、超稳定和 Biocompa 荧光有机纳米颗粒

• 批准号: 7784089
• 负责人: Steven C. Zimmerman
• 金额: $ 26.24万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7784089
• 关键词: Affinity; Alkenes; Amines; Architecture; Biocompatible; Biological Process; Biology; Characteristics; Chemicals; Chemistry; Defect; Dendrimers; Diagnostic; Dyes; Encapsulated; Exhibits; Fluorescein; Fluorescein-5-isothiocyanate; Fluoresceins; Fluorescent Dyes; Glycols; Goals; Link; Medical; Medicine; Membrane; Membrane Proteins; Molecular; Molecular Biology; Oligonucleotides; One-Step dentin bonding system; Performance; Photobleaching; Polymers; Process; Property; Protocols documentation; Reaction; Scheme; Silicon; Site; Solubility; Staging; Structure; Surface; Tail; Toxic effect; Water; aqueous; base; chromophore; crosslink; design; fluorophore; functional group; glycidol; irradiation; nanoparticle; organic base; particle; polyglycerol; prevent; propargyl alcohol; public health relevance; surface coating; toxic metal

DESCRIPTION (provided by applicant): Fluorescent dyes and nanoparticles are widely used in chemistry, biology, and medicine but suffer from poor photostability or toxicity (nanoparticles). The goal of this proposal is to create ultra-stable, monovalent, organic nanoparticles or organic coated metallic/silicon nanoparticles (< 6 nm size) using recently discovered chemistry that allows polyglycerol dendrimers and hyperbranched polymers to be tightly cross-linked around a core structure. The polyglycerol surfaces will be allylated and cross-linked using the ring-closing metathesis (RCM) reaction, followed by surface dihydroxylation to create a water-soluble particle. This chemistry is colloquially referred to as "multi-layer shrink-wrapping." The goal of the shrink-wrapping is to chemically isolate the fluorophore or preexisting nanoparticle and thus: (1) prevent dye aggregation, which often diminishes its performance, (2) prevent its undesired association with membranes and other biomolecules, and, most importantly, (3) reduce or eliminate photobleaching, and (4) stabilize existing nanoparticles with a dense, biocompatible sheath. We propose that through extreme isolation of the fluorophore or nanoparticle it may function indefinitely, thereby enabling a range of applications not previously possible. The fluorescent nanoparticles, which are designed to be fully biocompatible, can exhibit a range of excitation and emission wavelengths. PUBLIC HEALTH RELEVANCE: Fluorescent dyes and nanoparticles are widely used in medical diagnostics and for understanding chemical and biological processes at the molecular and cellular level. However, the dyes degrade rapidly upon irradiation and many nanoparticles contain toxic metals or are inherently toxic because of their surface coating. We propose a new strategy for preparing organic-based, ultra-stable and biocompatible fluorescent nanoparticles.

描述（由申请人提供）：荧光染料和纳米颗粒广泛用于化学、生物学和医学，但具有较差的光稳定性或毒性（纳米颗粒）。该提案的目标是使用最近发现的化学方法来创建超稳定的单价有机纳米颗粒或有机涂覆的金属/硅纳米颗粒（< 6 nm尺寸），该化学方法允许聚甘油树枝状聚合物和超支化聚合物围绕核心结构紧密交联。聚甘油表面将使用闭环复分解（RCM）反应进行烯丙基化和交联，然后进行表面二羟基化以产生水溶性颗粒。这种化学物质通俗地称为“多层收缩包装”。“收缩包装的目标是化学隔离荧光团或预先存在的纳米颗粒，因此：（1）防止染料聚集，这通常会降低其性能，（2）防止其与膜和其他生物分子的不希望的关联，最重要的是，（3）减少或消除光漂白，以及（4）稳定现有的纳米颗粒与致密的，生物相容的鞘。我们提出，通过荧光团或纳米颗粒的极端隔离，它可以无限地发挥作用，从而实现一系列以前不可能的应用。被设计为完全生物相容的荧光纳米颗粒可以表现出一系列的激发和发射波长。 公共卫生相关性：荧光染料和纳米颗粒广泛用于医学诊断以及在分子和细胞水平上理解化学和生物过程。然而，染料在照射后迅速降解，并且许多纳米颗粒含有有毒金属或由于其表面涂层而具有固有毒性。我们提出了一种新的策略，用于制备有机基的，超稳定的和生物相容性的荧光纳米粒子。