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

说明(申请人提供)：荧光染料和纳米颗粒广泛应用于化学、生物和医学，但存在光稳定性差或毒性(纳米颗粒)的问题。这项提议的目标是利用最近发现的化学技术创造超稳定的单价有机纳米颗粒或有机包覆的金属/硅纳米颗粒(&lt；6 nm大小)，这种化学方法允许聚甘油树枝状大分子和超支化聚合物在核心结构周围紧密交联。聚甘油表面将通过闭环歧化(RCM)反应进行烯丙化和交联化，然后进行表面双羟基化以生成水溶性颗粒。这种化学作用被俗称为“多层收缩包装”。收缩包装的目的是用化学方法隔离荧光团或预先存在的纳米颗粒，从而：(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发生不必要的结合，最重要的是，(3)减少或消除光漂白，以及(4)用致密的、生物兼容的鞘稳定现有的纳米颗粒。我们认为，通过对荧光团或纳米颗粒的极端隔离，它可以无限发挥作用，从而使一系列以前不可能实现的应用成为可能。这种荧光纳米颗粒被设计为完全生物兼容，可以显示一系列激发和发射波长。 公共卫生相关性：荧光染料和纳米颗粒被广泛用于医学诊断以及在分子和细胞水平上了解化学和生物过程。然而，染料在照射后迅速降解，许多纳米颗粒含有有毒金属，或由于其表面涂层而固有有毒。我们提出了一种新的策略来制备有机基、超稳定和生物相容的荧光纳米颗粒。

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.