Gold Nanoparticle-Photosensitizer Conjugate Based Photodynamic Inactivation of Biofilm Producing Cells: Potential for Treatment of <i>C</i>. <i>albicans</i> Infection in BALB/c Mice

Background Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms. We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm. We also examined the photodynamic efficacy of photosensitizer (PS) conjugated GNPs (GNP-PS) to treat skin and oral C. albicans infection in BALB/c mice. Methods The biomimetically synthesized GNPs were conjugated to photosensitizers viz. methylene blue (MB) or toluidine blue O (TB). The conjugation of PSs with GNPs was characterized by spectroscopic and microscopic techniques. The efficacy of gold nanoparticle conjugates against C. albicans biofilm was demonstrated by XTT assay and microscopic studies. The therapeutic efficacy of the combination of the GNP conjugates against cutaneous C. albicans infection was examined in mouse model by enumerating residual fungal burden and histopathological studies. Results The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms. The mixture of GNPs conjugated to two different PSs significantly depleted the hyphal C. albicans burden against superficial skin and oral C. albicans infection in mice. Conclusion The GNP-PS conjugate combination exhibits synergism in photodynamic inactivation of C. albicans. The GNP conjugate based PDT can be employed effectively in treatment of cutaneous C. albicans infections in model animals. The antibiofilm potential of PDT therapy can also be exploited in depletion of C. albicans on medical appliances such as implants and catheters etc.背景 现有研究表明，光动力疗法（Photodynamic Therapy，PDT）可有效抑制产膜微生物。本研究探究了金纳米颗粒（gold nanoparticle，GNP）偶联光敏剂对白色念珠菌（Candida albicans）生物膜的光动力作用，并考察了光敏剂（photosensitizer，PS）偶联金纳米颗粒（GNP-PS）对BALB/c小鼠皮肤及口腔白色念珠菌感染的光动力治疗效果。 方法 本研究将仿生合成的金纳米颗粒与光敏剂——亚甲蓝（methylene blue，MB）或甲苯胺蓝O（toluidine blue O，TB）——进行偶联。通过光谱学与显微镜技术对光敏剂与金纳米颗粒的偶联产物进行表征。采用XTT试验与显微镜观察验证了金纳米颗粒偶联物对抗白色念珠菌生物膜的效能。在小鼠感染模型中，通过计数残留真菌负荷及组织病理学研究，考察了金纳米颗粒偶联物联合疗法对皮肤白色念珠菌感染的治疗效果。 结果 基于金纳米颗粒-光敏剂偶联物的光动力疗法可有效杀灭白色念珠菌浮游态细胞及生物膜内的菌丝形态菌体。偶联两种不同光敏剂的金纳米颗粒混合物可显著降低小鼠皮肤及口腔浅表白色念珠菌感染中的真菌菌丝负荷。 结论 金纳米颗粒-光敏剂偶联物联合疗法在白色念珠菌的光动力灭活中展现出协同作用。基于金纳米颗粒偶联物的光动力疗法可有效用于模型动物的皮肤白色念珠菌感染治疗。光动力疗法的抗生物膜潜能还可用于清除植入物、导管等医疗器具表面的白色念珠菌。