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

项目摘要/摘要 这项建议描述了一个研究和培训计划，以促进我在生物膜治疗方面的学术生涯。 为我向独立的过渡提供便利。在过去的几年里，我获得了广泛的科学知识 背景和多个领域的广泛研究经验，包括纳米材料的合成， 化学，基于基质的纳米晶体，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、大小和组成的纳米材料来治疗与生物膜相关的疾病。这 因此，我的提案旨在加强和多样化我的纳米材料合成和表征 技能，并辅以传染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，称为笼子中的武尔夫 纳米颗粒(WICN)，将笼状结构和核心结构的能力整合在一起，使其能够用作 用于光声成像、计算机断层扫描和光热疗法(PTT)的造影剂。使用这些 结构，我已经证明了它们的PTT性能受到形状、大小和等离子体激元的严重影响 纳米颗粒的性质。因此，系统地研究这些独特的疗法的应用 形态，特别是针对感染性疾病，是朝着改进纳米疗法迈出的重要一步。 为此，我在这里建议开发具有纳米壳、纳米笼或 增强光热行为的纳米帧形态和不同成分(银、金、铂和钯) 并产生有效和快速的龋齿、伤口和皮肤感染治疗(目标1，K99)。这 纳米粒子的光热效应使精确的空间控制和整个组织的照射成为可能，同时 一种快速治疗。所开发的形态将用于检测抗生物被膜的效果和 PTNP的体外生物相容性。为此，将评估PTNP的抗菌性能，以减少 口腔和伤口感染的同时加快了光消融率(目标2，K99-R00)，我会选择最多的 有效的配方，以跟踪体内研究(目标3，R00)。在目标1和目标2中获得的知识将 作为一种灵活、快速、低成本的治疗方法，可用于增强体内生物膜的光热消融 方法。我们将使用啮齿动物龋齿模型和切除伤口模型在动物模型上测试PTNP 研究光和热的产生对体内生物膜的影响。我们会确认光热效应 已开发的结构的处理和抗生物被膜效果可以替代广谱的使用 在近红外光照射下，使用抗生素治疗伤口感染、预防龋齿和杀灭细菌。 为了指导我的事业，我组建了一个多学科的指导团队。在伊利诺伊大学 科莫德博士(主要导师，纳米医学领域的领先科学家)，来自宾夕法尼亚州放射学 口腔正畸科古医生(联合导师，生物膜相关口腔疾病专家) 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，还 引导我过渡到独立。这些部门将提供资源和支持，开展 实验室研究，培养我的职业发展，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.