Targeted combinatiorial therapy for treatment of periodontal disease

牙周病的靶向联合治疗

• 批准号: 7660001
• 负责人: MARK j YOUNG
• 金额: $ 21.38万
• 依托单位: MONTANA STATE UNIVERSITY - BOZEMAN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7660001
• 关键词: Acids; Address; Animal Model; Antibodies; Area; Bacteria; Canis familiaris; Chlorhexidine; Collaborations; Communities; Complex; Consultations; Coupled; Development; Engineering; Enhancers; Equilibrium; Family; Genetic; Gingiva; Immune; Immune system; In Vitro; Life; Methods; Microbial Biofilms; Modality; Modeling; Periodontal Diseases; Periodontal Infection; Pharmaceutical Preparations; Photosensitizing Agents; Proteins; Research; School Dentistry; Structure; Surface; System; Testing; Tetracyclines; Tissues; antimicrobial; antimicrobial peptide; base; bone loss; chemical genetics; combinatorial; design; effective therapy; killings; member; microbial community; nano; nanomaterials; oxidation; pathogen; public health relevance; research study; response; tool

DESCRIPTION (provided by applicant): An emerging concept is that the complex microbial communities that comprise periodontal consortia consist of both beneficial and pathogenic species. The implication is that periodontal disease can be treated by selectively eliminating putative pathogens, while minimizing the destruction of the commensal members of the community. We propose to engineer a family of nanoplatforms to target photosensitizers (PS) and PS/drug or antimicrobial peptide pairs to periodontal pathogens. We will test the hypothesis that the selective killing of targeted PS can be significantly enhanced by appropriate PS/drug or PS/antimicrobial peptide combinations. We will engineer nanoplatforms known as protein cages to implement our design strategy. In preliminary studies we have developed methods to target and kill biofilm-forming pathogens with protein cages functionalized with a photosensitizer (PS). In parallel, we developed a method for triggered release of a drug coupled to a protein cage. We will build upon this expertise to fabricate multifunctional nanoplatforms for targeted combinatorial therapy. The ability of our engineered nanoplatforms to selectively kill periodontal pathogens will be characterized in planktonic and established biofilm in vitro systems. We will determine which combinations of PS and enhancer are most effective in producing additive or synergistic killing of pathogens while maintaining selectivity. The specific aims (SA) are organized in terms of three combinations of treatment modalities: SA1) Targeted PS combined with non-targeted broad spectrum antimicrobials; SA2) Targeted PS combined with targeted triggered release of two types of broad spectrum antimicrobials and SA3) Targeted PS combined with an antimicrobial peptide. The strength of our research team lies in the combined expertise of two centers: the Center for BioInspired Nanomaterials and the Center for Biofilm Engineering. We have specifically designed the experiments so that the most promising systems can be tested in an animal model of periodontal disease. PUBLIC HEALTH RELEVANCE: The bone loss and tissue destruction that accompany periodontal disease are caused by the response of the immune system to bacteria. However, we know that the immune system can live in harmony with many types of bacteria. Our research will provide a tool to selectively eliminate bacteria suspected of causing immune malfunction while sparing bacteria thought to be beneficial.

描述（由申请人提供）：一个新兴的概念是构成牙周财团的复杂微生物群落由有益和致病物种组成。这意味着可以通过选择性地消除推定的病原体来治疗牙周疾病，同时最大程度地减少社区共生成员的破坏。我们建议将纳米植物的家族培养为靶向光敏剂（PS），PS/药物或抗菌肽对靶向牙周病原体。我们将检验以下假设：通过适当的PS/药物或PS/抗菌肽组合，可以显着增强目标PS的选择性杀害。我们将设计称为蛋白质笼的纳米植物，以实施我们的设计策略。在初步研究中，我们开发了使用光敏剂（PS）官能化的蛋白质笼子靶向和杀死生物膜形成的病原体的方法。同时，我们开发了一种触发与蛋白质笼子的药物释放的方法。我们将基于这些专业知识，以制造用于靶向组合疗法的多功能纳米文化。我们工程的纳米植物有选择地杀死牙周病原体的能力将以浮游生物和已建立的生物膜在体外系统中进行表征。我们将确定哪种PS和增强剂的组合在维持选择性的同时，最有效地产生了对病原体的累加或协同杀害。特定目的（SA）是根据治疗方式组合的三种组合组织的：SA1）靶向PS与非靶向的宽光谱抗菌抗菌药物相结合； SA2）靶向PS结合了靶向触发两种类型的宽光谱抗菌剂和SA3）的靶向PS与抗菌肽结合。我们的研究团队的优势在于两个中心的联合专业知识：生物启发的纳米材料中心和生物膜工程中心。我们专门设计了实验，以便可以在牙周疾病的动物模型中测试最有希望的系统。 公共卫生相关性：牙周疾病伴随的骨质流失和组织破坏是由免疫系统对细菌的反应引起的。但是，我们知道免疫系统可以与多种细菌和谐相处。我们的研究将提供一种工具，以选择性地消除涉嫌引起免疫功能的细菌，同时保留被认为是有益的细菌。