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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结/文摘