Abstract:
Many pathogenic bacteria are getting more and more resistant against antibiotic treatment and even become up to 1.000× times more resilient in the form of a mature biofilm. Thus, one is currently prospecting for alternative methods for treating microbial infections, and photodynamic therapy is a highly promising approach by creating so-called reactive oxygen species (ROS) produced by a photosensitizer (PS) upon irradiation with light. Unfortunately, the unspecific activity of ROS is also problematic as they are harmful to healthy tissue as well. Notably, one knows that uncontrolled existence of ROS in the body plays a major role in the development of cancer. These arguments create need for advanced theranostic materials which are capable of autonomous targeting and detecting the existence of a biofilm, followed by specific activation to combat the infection. The focus of this contribution is on mesoporous organosilica colloids functionalized by orthogonal and localized click-chemistry methods. The external zone of the particles is modified by a dye of the Hoechst family. The particles readily enter a mature biofilm where adduct formation with extracellular DNA and a resulting change in the fluorescence signal occurs, but they cannot cross cellular membranes such as in healthy tissue. A different dye suitable for photochemical ROS generation, Acridine Orange, is covalently linked to the surfaces of the internal mesopores. The spectral overlap between the emission of Hoechst with the absorption band of Acridine Orange facilitates energy transfer by Förster resonance with up to 88% efficiency. The theranostic properties of the materials including viability studies were investigated in vitro on mature biofilms formed by Pseudomonas fluorescens and prove the high efficacy.
摘要:
许多致病菌对抗生素治疗的抗性越来越强,甚至以成熟生物膜的形式变得更具弹性1.000倍。因此,目前正在寻找治疗微生物感染的替代方法,光动力疗法是一种非常有前途的方法,通过在光照射时产生由光敏剂(PS)产生的所谓活性氧(ROS)。不幸的是,ROS的非特异性活性也是有问题的,因为它们也对健康组织有害。值得注意的是,人们知道,体内ROS的不受控制的存在在癌症的发展中起着重要作用。这些论点产生了对能够自主靶向和检测生物膜存在的先进疗法材料的需求,然后进行特异性激活以对抗感染。这一贡献的重点是通过正交和局部点击化学方法官能化的介孔有机二氧化硅胶体。颗粒的外部区域由Hoechst家族的染料改性。颗粒容易进入成熟的生物膜,在那里与细胞外DNA形成加合物并发生荧光信号的变化。但是它们不能穿过细胞膜,比如健康组织。一种适用于光化学ROS产生的不同染料,吖啶橙,共价连接到内部中孔的表面。Hoechst的发射与吖啶橙的吸收带之间的光谱重叠促进了Förster共振的能量转移,效率高达88%。在体外研究了由荧光假单胞菌形成的成熟生物膜上的材料的治疗特性,包括活力研究,并证明了高功效。