Highly-Integrated Ultrasmall and Bright Fluorescent Silica Particle Architectures

研究项目1 高集成度超小发光二氧化硅颗粒 用于癌症诊断的不同尺寸、几何形状和组成的架构 和治疗学 1.项目摘要/摘要 这个基础研究/发现项目（RP 1）的首要目标是首先探索，然后优化新的 超小（<10 nm）荧光核-壳二氧化硅纳米颗粒（NP）和环（C ′/AC ′点和C 环），其在水中合成并用作靶向诊断和治疗探针以检测和治疗 各种癌症，特别是黑色素瘤。该项目的一个具体目标是调查 人黑色素瘤（M21）异种移植物中的药代动力学（PK）、肾清除率和肿瘤与背景比值 作为尺寸（~6- 15 nm，即肾清除率的截止值约为~10 nm），形状（球形， 环）和表面化学（配体数）。该项目的主要里程碑包括综合颗粒 使用成像、散射和光谱技术的阵列进行表征。而不是研究 生物学特性仅基于平均颗粒特性的批次间变化，RP 1将 采用高分辨率分析工具（GPC和HPLC）的组合来分析和分离不同的 来自单个颗粒合成批次的级分。RP 1的一个具体目标是解决一个最重要的问题， 纳米材料与生物系统相互作用的基本但尚未解决的问题-即 材料异质性的问题，以批次间变化和批次内变化的形式， 粒度分布和表面组成，调节PK、清除率曲线和靶点-背景 比率。该RP 1的粒子结果将馈送到所有其他RP 2 -4，从而覆盖整个诊断和 该中心的治疗地图。

RESEARCH PROJECT 1 HIGHLY-INTEGRATED ULTRASMALL AND BRIGHT FLUORESCENT SILICA PARTICLE ARCHITECTURES OF VARYING SIZE, GEOMETRY, AND COMPOSITION FOR CANCER DIAGNOSTICS AND THERAPEUTICS 1. Project Abstract/Summary The overarching goal of this basic research/discovery project (RP1) is to first explore and then optimize novel classes of ultrasmall (<10 nm) fluorescent core-shell silica nanoparticles (NPs) and rings (C'/AC' dots and C rings) that are synthesized in water and used as targeted diagnostic and therapeutic probes to detect and treat various types of cancer, in particular melanoma. A specific goal of this project is to investigate alterations in pharmacokinetics (PK), renal clearance, and tumor-to-background ratios in human melanoma (M21) xenograft models as a function of size (~6-15nm, i.e. around the cut off of ~10 nm for renal clearance), shape (spheres, rings), and surface chemistry (ligand number). Major milestones of the project include comprehensive particle characterization using an array of imaging, scattering, and spectroscopic techniques. Rather than studying biological properties solely on the basis of batch-to-batch variations in average particle properties, RP1 will employ a combination of high-resolution analytical tools (GPC and HPLC) to analyze and separate different fractions from individual particle synthesis batches. A specific goal of RP1 is to address one of the most fundamental, yet unresolved, problems of nanomaterials interactions with biological systems - namely the question of how material heterogeneity, in the form of batch-to-batch variations and variations within a batch, in particle size distributions and surface composition, modulates PK, clearance profiles, and target-to-background ratios. Particle outcomes of this RP1 will feed into all other RPs2-4 thereby covering the entire diagnostic and therapeutic map of the Center.