Selective Imaging and Eradication of Activated Macrophages Using Bio-conjugated Plasmon-resonant Gold Nanorods

本提案旨在开发一种利用功能化金纳米棒作为成像和光热剂，通过近红外激光照射靶向和根除动脉粥样硬化斑块中的巨噬细胞的方法。初步研究表明，利用八精氨酸（R8）肽偶联的金纳米棒，可以在体外对活化的原代巨噬细胞进行双光子发光成像和光学热疗。通过控制激光功率和照射时间，膜联蛋白V染色证实它们能够诱导巨噬细胞凋亡。假设是，激光照射积聚在斑块中的纳米棒可以诱导巨噬细胞凋亡，而对身体其他部分的毒性最小。这一假设将在体内水平上用ApoE缺陷小鼠进行验证，目的如下。(1)功能化金纳米棒延长血液循环时间，选择性靶向动脉粥样硬化斑块中的巨噬细胞。(2)测定功能化金纳米棒的血液停留时间、生物分布和器官毒性。(3) ApoE缺陷小鼠动脉粥样硬化斑块巨噬细胞的光学热疗。

CBET-0828832ChengThis proposal aims to develop a method that employs functionalized gold nanorods as an imaging and photothermal agent to target and eradicate macrophages in an atherosclerotic plaque by near infrared laser irradiation. preliminary studies have demonstrated two-photon luminescence imaging and optical hyperthermia of activated primary macrophages in vitro by gold nanorods conjugated with octaarginine (R8) peptides. By controlling the laser power and irradiation time, they have been able to induce apoptosis of macrophages confirmed by annexin V staining. The hypothesis is that laser irradiation of nanorods accumulated in a plaque could induce apoptosis of macrophages with minimal toxicity to the rest of the body. This hypothesis will be tested at the in vivo level using ApoE deficient mice with the following objectives. (1) Functionalize gold nanorods for prolonged blood circulation time and selective targeting to macrophages in an atherosclerotic plaque. (2) Determine the blood residence time, biodistribution, and organ toxicity of functionalized gold nanorods. (3) Optical hyperthermia of macrophages in atherosclerotic plaques of ApoE deficient mice.