Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
Virulence. 2011 Nov-Dec;2(6):509-20. doi: 10.4161/viru.2.6.17889. Epub 2011 Nov 1.
The story of prevention and control of infectious diseases remains open and a series of highly virulent pathogens are emerging both in and beyond the hospital setting. Antibiotics were an absolute success story for a previous era. The academic and industrial biomedical communities have now come together to formulate consensus beliefs regarding the pursuit of novel and effective alternative anti-infective countermeasures. Photodynamic therapy was established and remains a successful modality for malignancies but photodynamic inactivation has been transformed recently to an antimicrobial discovery and development platform. The concept of photodynamic inactivation is quite straightforward and requires microbial exposure to visible light energy, typically wavelengths in the visible region, that causes the excitation of photosensitizer molecules (either exogenous or endogenous), which results in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation. It is an area of increasing interest, as research is advancing i) to identify the photochemical and photophysical mechanisms involved in inactivation; ii) to develop potent and clinically compatible photosensitizer; iii) to understand how photoinactivation is affected by key microbial phenotypic elements (multidrug resistance and efflux, virulence and pathogenesis determinants, biofilms); iv) to explore novel delivery platforms inspired by current trends in pharmacology and nanotechnology; and v) to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.
传染病的防控故事仍在继续,一系列高毒力的病原体在医院内外不断出现。抗生素在过去是一个绝对的成功案例。现在,学术界和工业界的生物医学界已经联合起来,就寻求新型有效抗感染对策达成了共识。光动力疗法已经确立,并仍然是治疗恶性肿瘤的一种成功方法,但光动力失活最近已经转变为一种抗菌发现和开发平台。光动力失活的概念非常简单,需要微生物暴露于可见光能量下,通常是在可见光区域的波长,这会导致光敏剂分子(无论是外源性的还是内源性的)被激发,从而产生单线态氧和其他活性氧物质与细胞内成分反应,最终导致细胞失活。由于研究在以下几个方面取得了进展,该领域的兴趣日益增加:i)确定失活涉及的光化学和光物理机制;ii)开发有效且与临床兼容的光敏剂;iii)了解光失活如何受到关键微生物表型因素(多药耐药和外排、毒力和发病机制决定因素、生物膜)的影响;iv)探索基于药理学和纳米技术当前趋势的新型传递平台;v)确定临床环境之外的光失活应用,如环境消毒剂。