Photosensitizer (PS) mediated Photodynamic Therapy (PDT) is a preferred treatment modality for certain cancers. Some of the factors limiting the expansion of PDT to other clinical conditions are the aggregation of hydrophobic PS in aqueous media and the inefficient biodistribution of photosensitizers. Formulations containing the PS have overcome some of the limitations by controlling aggregation-dependent quenching of PS and by improving the biodistribution of PS. We report a photosensitizer delivery system with protein nanoparticles that does not involve any chemical modifications. Using Lactoferrin, an iron-carrying milk protein, as sole matrix and Chlorine e6 (Ce6), an FDA-approved PS. The nanoparticles were prepared by the water-in-oil emulsion method. The spectral and physical properties of the particles were analyzed. Production of reactive oxygen was enhanced in the formulations (LeN) compared to free Ce6 as indicated by the water-soluble and -insoluble dyes. LeN show a specific Ce6 release at low pH, which is an advantage in the acidic environment of tumors and in endosomes. The uptake and intracellular concentrations of Ce6 by SK-OV-3, estimated by confocal microscopy, FACS and fluorescence spectroscopy, were significantly higher with LeN compared to free Ce6. Upon light exposure, LeN showed a substantial decrease (>4 times) in Ce6 requirement compared to free Ce6 in its ability to cause light-mediated cell death in the SK-OV-3 and MDA-MD 231 cells. LeN were shown to be non-toxic to the cells even at concentrations ten times that used in the PDT study. Safety, efficient loading and significant uptake by cells and more importantly a significant decrease in IC₅₀ values demonstrate that LeN have potential in PDT.

中文翻译：

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装载氯霉素e6的乳铁蛋白纳米颗粒用于增强光动力治疗

光敏剂（PS）介导的光动力疗法（PDT）是某些癌症的首选治疗方式。限制PDT扩展至其他临床状况的一些因素是疏水性PS在水性介质中的聚集以及光敏剂的生物分布效率低下。含有PS的制剂通过控制PS的聚集依赖性猝灭和改善PS的生物分布，克服了一些局限性。我们报告了不包含任何化学修饰的蛋白质纳米颗粒的光敏剂递送系统。使用载铁蛋白乳铁蛋白作为唯一基质，并使用FDA批准的氯e6（Ce6）。通过油包水乳液法制备纳米颗粒。分析了颗粒的光谱和物理性质。如水溶性和不溶性染料所示，与游离的Ce6相比，制剂（LeN）中活性氧的产量得到了提高。LeN在低pH下显示特定的Ce6释放，这在肿瘤的酸性环境和内体中是一个优势。通过共聚焦显微镜，FACS和荧光光谱法估计，SK-OV-3对Ce6的摄取和细胞内浓度显着高于游离Ce6。暴露于光下后，LeN与游离Ce6相比，在引起SK-OV-3和MDA-MD 231细胞中光介导的细胞死亡的能力方面显示出与游离Ce6相比所需的Ce6需求量大幅减少（> 4倍）。甚至在PDT研究中使用的浓度是LeN的十倍时，LeN也显示出对细胞无毒。安全，_50个值表明LeN在PDT中具有潜力。