Novel Nanostructures for Topical Photodynamic Therapy

描述(申请人提供)：富勒烯是一类完全由碳原子组成的封闭笼状纳米材料。开发这些独特分子的医学用途已经引起了极大的关注。这项建议涉及富勒烯在抗菌光动力疗法中的开发，这是一种将无毒光敏剂与无害的可见光相结合以杀灭微生物细胞的非侵入性程序。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地针对特定细胞类型的光敏剂和控制被照射的区域来实现的。在第一阶段的研究中，合成了一些性能非常理想的富勒烯类光敏剂，并对其进行了测试。PS可灭活多种微生物(对革兰氏阳性菌、革兰氏阴性菌和真菌的杀灭率为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，只需要低水平的光照。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。测试还表明，富勒烯光敏剂的表现明显好于临床上常用的抗菌光敏剂。在第二阶段的研究中，将了解富勒烯的纳米级特性与它们选择性光灭活微生物的能力之间的关系，从而导致局部细菌和真菌感染治疗方法的商业开发。此外，将使用生物发光细菌和微光成像技术在感染伤口和烧伤的小鼠模型中测试PS对局部PDT的调节作用，以实时跟踪感染过程。抗菌光动力疗法可以作为一种新技术来对抗已经产生抗生素耐药性的病原菌。伤口感染每年影响数以百万计的美国人。随着抗生素耐药性的不断增加，人们寻求抗菌剂来治疗局部感染(细菌和真菌)，并在皮肤科、牙科和眼科应用。预计全球市场将达到30亿美元，这是一个重要的商业化机会。

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.