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: 10625065
• 负责人: Maryam Hajfathalian
• 金额: $ 9.15万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10625065
• 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.

项目概要/摘要 该提案描述了一项研究和培训计划，以促进我在生物膜治疗方面的学术生涯 并促进我向独立过渡。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丰富的研究经验，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 旨在开发具有不同形状、尺寸和成分的纳米材料，用于治疗生物膜相关疾病。这 因此，该提案旨在加强和多样化我的纳米材料合成和表征 技能，并通过感染性疾病和治疗方面的培训对其进行补充。 在我的博士后培训期间，我开发了一种独特的结构，称为“笼中武尔夫” 纳米粒子（WICN），整合了笼状结构和核心结构的能力，使其可以用作 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，我已经证明它们的 PTT 特性受到形状、尺寸和等离激元的严重影响 纳米粒子的特性。因此，系统地研究这些独特的治疗应用 形态学，特别是针对感染性疾病的形态学，是改进纳米疗法的必要步骤。 为此，我在这里建议开发具有纳米壳、纳米笼或纳米颗粒的新型光热纳米颗粒（PTNP） 增强光热行为的纳米框架形态和不同成分（Ag、Au、Pt 和 Pd） 并实现有效、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可以实现精确的空间控制和整个组织照射，同时 快速治疗。开发的形态将用于检查抗生物膜功效和 PTNP 的体外生物相容性。为此，将对 PTNP 的抗菌特性进行评估，以减少 口腔和伤口感染，同时加速光消融率（目标2，K99-R00），我会选择最 遵循（目标 3，R00）中的体内研究的有效配方。在目标 1 和 2 中获得的知识将 作为一种灵活、快速且低成本的治疗方法，可用于增强体内生物膜的光热消融 方法。我们将使用龋齿啮齿动物模型和切除伤口模型在动物模型中测试 PTNP 研究光和热的产生对体内生物膜的影响。我们将确认光热 发达结构的治疗和抗生物膜作用可以替代广谱的使用 抗生素可治愈伤口感染、预防龋齿并在近红外光照射下杀死细菌。 为了指导我完成这项事业，我组建了一个多学科的指导团队。在大学 宾夕法尼亚州，放射学科莫德博士（主要导师，纳米医学领先科学家） 正畸科 Dr. Koo（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，并且 指导我向独立过渡。这些部门将提供资源和支持来开展 实验室研究，促进我的职业发展以实现我的目标。

项目成果

Nisin and Nisin Probiotic Disrupt Oral Pathogenic Biofilms and Restore Their Microbiome Composition towards Healthy Control Levels in a Peri-Implantitis Setting.

乳链菌肽和乳链菌肽益生菌可破坏口腔致病性生物膜，并将其微生物组组成恢复到种植体周围炎环境中的健康控制水平。

• 发表时间: 2022-07-01
• 影响因子: 4.5
• 作者: Radaic, Allan;Brody, Hanna;Contreras, Fernando;Hajfathalian, Maryam;Lucido, Luke;Kamarajan, Pachiyappan;Kapila, Yvonne L
• 通讯作者: Kapila, Yvonne L

Optimized preparation pipeline for emergency phage therapy against Pseudomonas aeruginosa at Yale University.

耶鲁大学针对铜绿假单胞菌的紧急噬菌体治疗的优化制备流程。

• 发表时间: 2024-02-01
• 影响因子: 4.6
• 作者: Würstle, Silvia;Lee, Alina;Kortright, Kaitlyn E;Winzig, Franziska;An, William;Stanley, Gail L;Rajagopalan, Govindarajan;Harris, Zach;Sun, Ying;Hu, Buqu;Blazanin, Michael;Hajfathalian, Maryam;Bollyky, Paul L;Turner, Paul E;Koff, Jonathan L;C
• 通讯作者: C