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

通过复杂的贵金属纳米结构进行抗生物膜激光介导的光热烧蚀

• 批准号: 10215516
• 负责人: Maryam Hajfathalian
• 金额: $ 7.68万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10215516
• 关键词: Ablation; Affect; Animal Model; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Architecture; Area; Award; Bacteria; Behavior; Binding; Bladder; Body Surface; Cardiovascular Diseases; Cells; Chemistry; Clinical; Communicable Diseases; Competence; Complement; Complex; Contrast Media; Data; Dental Alloys; Dental caries; Dermatology; Development; Devices; Disease; Drug Delivery Systems; Effectiveness; Elements; Engineering; Excision; Exposure to; Extracellular Matrix; Formulation; Fostering; Generations; Goals; Heart Valves; Image; In Vitro; Infection; Infectious Skin Diseases; Knowledge; Laboratory Research; Lasers; Light; Lighting; Lung; Malignant Neoplasms; Mediating; Mentors; Metals; Methods; Microbial Biofilms; Morphology; Mouth Diseases; Nanostructures; Nanotechnology; New Agents; Organ; Orthodontics; Patients; Pennsylvania; Phase; Polymers; Process; Property; Public Health; Radiology Specialty; Reporting; Research; Research Activity; Research Proposals; Research Training; Resolution; Resources; Rodent; Rodent Model; Safety; Scientist; Shapes; Skin; Skin Tissue; Staphylococcus aureus; Streptococcus mutans; Structure; Surface; Techniques; Testing; Therapeutic; Therapeutic Studies; Thermal Ablation Therapy; Tissues; Tooth structure; Training; Training Programs; Transition Elements; Treatment Cost; Universities; Virulent; Wound Infection; Wound models; X-Ray Computed Tomography; antimicrobial; base; biomaterial compatibility; career; career development; chemical property; chronic infection; colloidal nanoparticle; design; disorder control; experience; experimental study; extracellular; flexibility; fluorescence imaging; improved; in vivo; in vivo evaluation; in vivo imaging; innovation; irradiation; light effects; medical implant; microbial; microorganism; multidisciplinary; nano; nanocage; nanocrystal; nanomaterials; nanomedicine; nanoparticle; nanoshell; nanotherapeutic; novel; oral infection; oral pathogen; pathogen; photoacoustic imaging; photothermal therapy; physical property; plasmonics; post-doctoral training; prevent; skills; skin disorder; soft tissue; time interval; wound; wound healing

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.

项目摘要/摘要 该建议描述了一项研究和培训计划，以提高我在生物膜治疗领域的学术生涯 并促进我向独立的过渡。在过去的几年中，我获得了广泛的科学 背景和广泛的研究经验，包括纳米材料的合成，包括 化学，基于底物的纳米晶体，纳米医学，体外和体内成像。我的长期职业目标 是为生物膜相关疾病的形状，大小和组成不同的纳米材料。这 因此，建议旨在加强和多样化我的纳米材料合成和特征 技能，通过感染疾病和疗法的培训来补充他们。 在我的博士后训练期间，我开发了一个独特的结构，称为瓦尔夫（Wulff） 纳米颗粒（WICN）整合了笼子和核心结构的能力，以便它们用作 光声成像，计算机断层扫描和光热疗法（PTT）的对比剂。使用这些 结构，我已经证明了它们的PTT性质受形状，大小和等离子的严重影响 纳米颗粒的特性。因此，系统地研究这些独特的疗法应用 形态，尤其是针对感染疾病的形态，是朝着改善纳米疗法迈出的一步。 为此，我建议用纳米壳，纳米或 纳米形态和不同的成分（AG，AU，PT和PD）增强光热行为 并导致有效且快速的龋齿，伤口和皮肤感染治疗（AIM 1，K99）。这 纳米颗粒的光热效应可以实现精确的空间控制和整个组织照射，同时是 快速治疗。开发的形态将用于检查抗生物膜的功效和 PTNP体外的生物相容性。在此目标中，将对PTNP的抗菌特性进行评估以减少 在加速光电率的同时，口腔和伤口感染（AIM 2，K99-R00），我将选择最多 有效的表述遵循（AIM 3，R00）的体内研究。目标1和2中获得的知识将 应用于增强体内生物膜的光热消融，作为灵活，快速和低成本的处理 方法。我们将使用龋齿和弹性伤口模型的啮齿动物模型在动物模型中测试PTNP 研究光和热量产生对体内生物膜的影响。我们将确认光热 开发结构的治疗和抗生物膜的效应可以代替使用广谱 抗生素可以治愈伤口感染，防止龋齿并杀死细菌，同时用NIR光照射。 为了指导我在这项工作中，我组建了一个多学科的指导团队。在大学 放射学 牙齿矫正部门的Koo博士（生物膜相关的口腔疾病专家） 皮肤科系的Grice博士（Co-Contor，生物膜相关的皮肤病专家）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 指导我过渡到独立。这些部门将提供资源和支持以进行 实验室研究，并促进我的职业发展以实现自己的目标。