Anti-biofilm laser-mediated photothermal ablation via complex noble metal nanostructures

项目概要/摘要 这个建议描述了一个研究和培训计划，以促进我的学术生涯在生物膜治疗 帮助我向独立过渡在过去的几年里，我获得了广泛的科学知识 在多个领域的背景和广泛的研究经验，包括纳米材料的合成， 化学、基于基底的纳米晶体、纳米医学、体外和体内成像。我的长期职业目标 是开发不同形状、大小和成分的纳米材料，用于生物膜相关疾病。这 因此，我的建议旨在加强和多样化我的纳米材料的合成和表征 技能，并辅之以感染疾病和治疗方面的培训。 在我的博士后培训期间，我开发了一种独特的结构，称为Wulff笼 纳米颗粒（WICN），其整合了笼状结构和核心结构的能力，以允许它们用作 用于光声成像、计算机断层扫描和光热治疗（PTT）的造影剂。使用这些 结构，我已经表明，它们的PTT性能受到形状，大小和等离子体激元的严重影响。 纳米粒子的性质。因此，系统地研究这些独特的治疗应用， 纳米形态学的研究，特别是针对感染性疾病的研究，是改善纳米治疗的必要步骤。 为此，在这里，我建议开发新的光热纳米粒子（PTNP）与纳米壳，纳米笼或 纳米框架形态和不同的成分（Ag、Au、Pt和Pd）增强光热行为 并导致有效和快速的龋齿、伤口和皮肤感染治疗（目标1，K99）。这 纳米颗粒的光热效应使得能够进行精确的空间控制和整个组织照射，同时 快速治疗。所开发的形态将用于检查抗生物膜功效， PTNP在体外的生物相容性。在这个目标中，将评估PTNP的抗菌性能，以减少 口腔和伤口感染，同时加快光消融率（目标2，K99-R 00），我将选择最 有效的制剂，以遵循体内研究（目标3，R 00）。在目标1和2中获得的知识将 作为一种灵活、快速和低成本的治疗方法， 法我们将使用龋齿的啮齿动物模型和切除伤口模型在动物模型中测试PTNP 研究光和热产生对体内生物膜的影响。我们将确认光热 处理和开发的结构的抗生物膜效果可以替代使用广谱 在使用NIR光照射时，抗生素可以治愈伤口感染，预防龋齿并杀死细菌。 为了指导我完成这项工作，我组建了一个多学科的指导小组。电修 宾夕法尼亚州，来自放射科的Cormode博士（主要导师，纳米医学的领先科学家） 口腔正畸科顾医生（共同导师，生物膜相关口腔疾病专家） 和来自皮肤科的Grice博士（共同导师，生物膜相关皮肤病专家）将 继续指导我进行体外和体内实验。他们将支持我的研究活动， 引导我走向独立这些部门将提供资源和支持， 实验室研究，并促进我的职业发展，以实现我的目标。

Project Summary/Abstract This proposal describes a research and training program to advance my academic career in biofilm treatment and facilitate my transition towards independence. Over the past years, I have acquired a broad scientific background and extensive research experience in multiple fields, including synthesis of nanomaterials, chemistry, substrate-based nanocrystals, nanomedicine, in vitro and in vivo imaging. My long-term career goal is to develop nanomaterials with different shapes, sizes, and compositions for biofilm-associated diseases. This proposal was therefore designed to strengthen and diversify my nanomaterial synthesis and characterization skills, complementing them with training in infection diseases and therapies. During my postdoctoral training period, I have developed a unique structure termed Wulff in cage nanoparticles (WICN) that integrate the competencies of both cage and core structures to allow their use as contrast agents for photoacoustic imaging, computed tomography and photothermal therapy (PTT). Using these structures, I have shown that their PTT properties are critically affected by shape, size and the plasmonic properties of nanoparticles. Therefore, systematically studying the therapeutics applications of these unique morphologies, particularly towards infection diseases, is an imperative step towards improving nanotherapeutics. To that end, here I propose to exploit new photothermal nanoparticles (PTNP) with nanoshell, nanocage or nanoframe morphologies and different compositions (Ag, Au, Pt, and Pd) which enhance photothermal behavior and result in effective and rapid dental caries, wound and skin infection treatments (Aim 1, K99). This photothermal effect of nanoparticles enables both precise spatial control and whole tissue irradiation, while being a rapid treatment. The developed morphologies will be used to examine the anti-biofilm efficacy and biocompatibility of the PTNP in vitro. In this aim, PTNP will be assessed for their antibacterial properties to reduce oral and wound infections while accelerating the photoablation rates (Aim 2, K99-R00), I will select the most effective formulation to follow the in vivo research in (Aim 3, R00). The knowledge acquired in Aims 1 and 2 will be applied to enhance the photothermal ablation of biofilms in vivo as a flexible, fast and low cost treatment method. We will test PTNP in an animal model using rodent models of dental caries and excisional wound model to investigate the effect of light and heat generation on biofilms in vivo. We will confirm that photothermal treatment and the anti-biofilm effect of developed structures could be a substitute to the use of broad-spectrum antibiotics to heal wound infection, prevent dental caries and kill the bacteria while irradiating with NIR light. To guide me in this undertaking, I have assembled a multidisciplinary mentoring team. At University of Pennsylvania, Dr. Cormode (Primary Mentor, a leading scientist in Nanomedicine) from the Radiology department , Dr. Koo (Co-mentor, biofilm-associated oral diseases expert) from the Department of Orthodontics and Dr. Grice (Co-mentor, biofilm-associated skin diseases expert) from the Department of Dermatology will continue mentoring me on in vitro and in vivo experiments. They will support my research activities and also guide my transition to independence. These departments will provide resources and support to conduct laboratory research, and foster my career development to achieve my goals.