Department of Macromolecular Science and Engineering, Case Western Reserve University , 2100 Adelbert Road, Cleveland, Ohio 44106, United States.
Department of Dermatology, Case Skin Disease Research Center, Case Western Reserve University/University Hospitals Cleveland Medical Center , Cleveland, Ohio 44106, United States.
Biomacromolecules. 2017 Feb 13;18(2):379-385. doi: 10.1021/acs.biomac.6b01436. Epub 2017 Jan 24.
Fungi account for billions of infections worldwide. The second most prominent causative agent for fungal infections is Candida albicans (C. albicans). As strains of fungi become resistant to antifungal medications, new treatment modalities must be investigated to combat these infections. One approach is to employ photodynamic therapy (PDT). PDT utilizes a photosensitizer, light, and cellular O to produce reactive oxygen species (ROS), which then induce oxidative stress resulting in apoptosis. Silicon phthalocyanine Pc 4 is a photosensitizer that has exhibited success in clinical trials for a myriad of skin diseases. The hydrophobic nature of Pc 4, however, poses significant formulation and delivery challenges in the use of this therapy. To mitigate these concerns, a drug delivery vehicle was synthesized to better formulate Pc 4 into a viable PDT agent for treating fungal infections. Utilizing poly(amidoamine) dendrimers as the framework for the vehicle, ∼13% of the amine chain ends were PEGylated to promote water solubility and deter nonspecific adsorption. In vitro studies with C. albicans demonstrate that the potency of Pc 4 was not hindered by the dendrimer vehicle. Encapsulated Pc 4 was able to effectively generate ROS and obliterate fungal pathogens upon photoactivation. The results presented within describe a nanoparticulate delivery vehicle for Pc 4 that readily kills drug-resistant C. albicans and eliminates solvent toxicity, thus, improving formulation characteristics for the hydrophobic photosensitizer.
真菌在全球范围内引发了数十亿例感染。真菌感染的第二大主要病原体是白色念珠菌（C. albicans）。随着真菌菌株对抗真菌药物产生耐药性，必须研究新的治疗方法来对抗这些感染。一种方法是采用光动力疗法（PDT）。PDT 使用光敏剂、光和细胞内的 O 来产生活性氧（ROS），然后诱导氧化应激导致细胞凋亡。硅酞菁 Pc 4 是一种光敏剂，在临床试验中已成功用于治疗多种皮肤病。然而，Pc 4 的疏水性给这种疗法的制剂和输送带来了重大挑战。为了减轻这些担忧，合成了一种药物输送载体，以便更好地将 Pc 4 制成一种可行的 PDT 药物，用于治疗真菌感染。利用聚（酰胺-胺）树枝状大分子作为载体的框架，约 13%的胺链末端进行了 PEG 化以提高水溶性并阻止非特异性吸附。与白色念珠菌的体外研究表明，树枝状大分子载体并未阻碍 Pc 4 的效力。包封的 Pc 4 能够在光激活时有效产生 ROS 并消灭真菌病原体。本文介绍了一种用于 Pc 4 的纳米颗粒药物输送载体，它能够轻易杀死耐药性的 C. albicans 并消除溶剂毒性，从而改善了疏水性光敏剂的制剂特性。
