Single Molecule Studies of Unimolecular Nanocarriers

描述（由申请人提供）：单分子光谱技术将用于测定受控药物递送系统、单分子两亲性纳米载体（UAN）的物理性质。我们将把UAN聚合物核心的物理性质与其溶解和递送药物分子的能力联系起来。该项目的具体目标是了解保护和溶解药物分子的包封过程，并确定药物分子的分布和递送过程; UAN不仅可用于溶解疏水性药物分子，还可保护其免受环境降解。这些研究还将有助于确定哪些因素将使UAN能够更好地通过细胞膜递送药物。研究包封的主要技术将是环境敏感的本体和单分子时间分辨光谱学。将使用一系列具有改性聚合物核的UAN来确定聚合物的不同柔性如何影响荧光探针分子的增溶。为了评估UAN通过渗透膜优先递送药物的能力，将使用扫描共聚焦显微镜和单分子检测对生物活性分子向脂质体的实际递送进行动态成像。

DESCRIPTION (provided by applicant): Single molecule spectroscopic techniques will be used to assay the physical properties of controlled drug delivery systems, unimolecular amphiphilic nanocarriers (UAN). We will relate the physical properties of the UAN's polymer core to its ability to solubilize and deliver drug molecules. The specific aims of this project are to understand the encapsulation process that protects and solubilizes the drug molecule, and to determine the process of distribution and delivery of the drug molecule; a UAN can be used not only to solubilize a hydrophobic drug molecule, but also to protect it from environmental degradation. These studies will also help determine what factors will enable the UAN to better deliver the drug through cell membranes. The principle techniques in studying encapsulation, will be environmentally sensitive bulk and single molecule time resolved spectroscopy. A series of UAN's with modified polymer cores will be used to determine how the different flexibilities of the polymer effect solubilization of a fluorescent probe molecule. To assess the ability of a UAN to preferentially deliver drugs by permeating a membrane, actual delivery of bioactive molecules to liposomes will be dynamically imaged using scanning confocal microscopy and single molecule detection.