Novel Nanostructures for Topical Photodynamic Therapy

用于局部光动力治疗的新型纳米结构

• 批准号: 7474646
• 负责人: Sanjiv Lalwani
• 金额: $ 40万
• 依托单位: LYNNTECH, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474646
• 关键词: Accounting; Acne; Aerosols; Affect; Aftercare; Agreement; American; Animal Model; Antibiotic Resistance; Antimicrobial Resistance; Architecture; Area; Attention; Bacteria; Bacterial Infections; Binding; Biological; Burn Trauma; Burn injury; Candida albicans; Candidiasis; Carbon; Cell Nucleus; Cell Wall; Cells; Class; Clinical; Collaborations; Communicable Diseases; Condition; Data; Dentistry; Dermatology; Development; Disclosure; Disease; Escherichia coli; Evaluation; Focal Infection; Fullerenes; General Hospitals; Goals; Government; Gram-Negative Bacteria; Gram-Positive Bacteria; Histocompatibility Testing; Image; Infection; Infectious Agent; Injection of therapeutic agent; Intellectual Property; Invasive; Investigation; Isomerism; Laboratories; Lasers; Lead; Legal patent; Letters; Light; Lighting; Localized; Mammalian Cell; Manufacturer Name; Marketing; Massachusetts; Mediation; Medical; Membrane; Methods; Microbe; Mycoses; Nail plate; Nanostructures; Normal Cell; Numbers; Ophthalmology; Outcome; Permeability; Persons; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Photochemotherapy; Photosensitizing Agents; Porphyrins; Positioning Attribute; Predisposition; Procedures; Process; Property; Pseudomonas aeruginosa; Purpose; Range; Reactive Oxygen Species; Research; Role; Route; Singlet Oxygen; Skin; Source; Structure; Surgical incisions; Techniques; Testing; Tetrapyrroles; Time; Tissues; Tolonium chloride; Topical application; Trademark; Treatment Efficacy; United States; Visible Radiation; Wound Infection; antimicrobial; authority; bacteriochlorin; base; biomaterial compatibility; cancer cell; cancer therapy; cationic fullerene; cell type; chlorin; commercialization; cost; cytotoxicity; design; fullerene C60; functional group; fungus; interstitial; killings; medical schools; microbial; microorganism; mouse model; nanomaterials; nanoscale; novel; pathogenic bacteria; phthalocyanine; pre-clinical; research and development; scaffold; size; therapy development; tumor; uptake; water solubility

DESCRIPTION (provided by applicant): Fullerenes are a class of closed-cage nanomaterials comprised exclusively of carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules. This proposal concerns the development of fullerenes in antimicrobial photodynamic therapy, a non-invasive procedure that combines a non-toxic photosensitizer with harmless visible light to kill microbial cells. An advantage of photodynamic therapy is its high level of selectivity. This is achieved by using photosensitizers that selectively target specific cell types and by controlling the area that is illuminated. In the Phase I study, a number of fullerene-based photosensitizers with highly desirable properties were synthesized and tested. The PS inactivated a broad spectrum of microbes (6 log reduction of gram positive bacteria, gram negative bacteria and fungi). The Phase I results are particularly encouraging because the fullerene photosensitizers were effective at low concentrations and needed only low levels of illumination. In addition, under conditions where bacterial cells were killed, mammalian cells were unharmed. Tests also showed that the fullerene photosensitizers performed substantially better than an antimicrobial photosensitizer commonly used in clinical practice. In the Phase II study, an understanding of the relationship between the nanoscale properties of fullerenes and their ability to selectively photoinactivate microorganisms will be developed, leading to the commercial development of treatments for localized bacterial and fungal infections. In addition, the PS will be tested for the mediation of topical PDT in mouse models of infected wounds and burns using bioluminescent bacteria and low-light imaging to follow infection progress in real time. Antimicrobial photodynamic therapy can serve as a new technique to combat pathogenic bacteria that have developed antibiotic resistance. Wound infections affect millions of Americans each year. With ever increasing antibiotic resistance, antimicrobials are sought for treatment of localized infections (bacterial and fungal) with applications in dermatology, dentistry, and ophthalmology. A global market of $3 billion dollars is projected, representing a significant opportunity for commercialization.

描述（由申请人提供）：富勒烯是一类完全由碳原子组成的闭笼纳米材料。大量的注意力集中在开发这些独特分子的医疗用途上。该建议涉及富勒烯在抗菌光动力疗法中的发展，这是一种非侵入性的方法，将无毒光敏剂与无害的可见光结合起来杀死微生物细胞。光动力疗法的一个优点是它的高选择性。这是通过使用选择性靶向特定细胞类型的光敏剂和通过控制照射区域来实现的。在第一阶段的研究中，合成并测试了一些具有非常理想性能的富勒烯基光敏剂。PS灭活广泛的微生物（革兰氏阳性菌，革兰氏阴性菌和真菌减少6对数）。第一阶段的结果特别令人鼓舞，因为富勒烯光敏剂在低浓度下有效，只需要低水平的照明。此外，在细菌细胞被杀死的条件下，哺乳动物细胞没有受到伤害。试验还表明，富勒烯光敏剂的性能大大优于临床实践中常用的抗菌光敏剂。在第二阶段的研究中，富勒烯的纳米级特性与其选择性光灭活微生物的能力之间的关系将得到发展，从而导致局部细菌和真菌感染治疗的商业化发展。此外，PS将在感染伤口和烧伤的小鼠模型中进行局部PDT介导测试，使用生物发光细菌和低光成像来实时跟踪感染进展。抗菌光动力疗法可以作为一种新的技术来对抗已经产生抗生素耐药性的致病菌。伤口感染每年影响数百万美国人。随着抗生素耐药性的不断增加，抗菌药物被用于治疗局部感染（细菌和真菌），应用于皮肤科、牙科和眼科。预计全球市场将达到30亿美元，这是商业化的重要机会。

项目成果

Antimicrobial Photodynamic Therapy with Functionalized Fullerenes: Quantitative Structure-activity Relationships.

• DOI: 10.4172/2157-7439.1000109
• 发表时间: 2011-04-01
• 期刊: Journal of nanomedicine & nanotechnology
• 作者: Mizuno K;Zhiyentayev T;Huang L;Khalil S;Nasim F;Tegos GP;Gali H;Jahnke A;Wharton T;Hamblin MR
• 通讯作者: Hamblin MR

Photodynamic therapy with a cationic functionalized fullerene rescues mice from fatal wound infections.

• DOI: 10.2217/nnm.10.98
• 发表时间: 2010-12
• 期刊: Nanomedicine (London, England)
• 作者: Lu Z;Dai T;Huang L;Kurup DB;Tegos GP;Jahnke A;Wharton T;Hamblin MR
• 通讯作者: Hamblin MR