PDF(Pubmed)
Abstract：
Photodynamic therapy (PDT) is a well-known cancer therapy that utilizes light to excite a photosensitizer and generate cytotoxic reactive oxygen species (ROS). The efficacy of PDT primarily depends on the photosensitizer and oxygen concentration in the tumor. Hypoxia in solid tumors promotes treatment resistance, resulting in poor PDT outcomes. Hence, there is a need to combat hypoxia while delivering sufficient photosensitizer to the tumor for ROS generation. Here we showcase our unique theranostic perfluorocarbon nanodroplets as a triple agent carrier for oxygen, photosensitizer, and indocyanine green that enables light triggered spatiotemporal delivery of oxygen to the tumors. We evaluated the characteristics of the nanodroplets and validated their ability to deliver oxygen via photoacoustic monitoring of blood oxygen saturation and subsequent PDT efficacy in a murine subcutaneous tumor model. The imaging results were validated with an oxygen sensing probe, which showed a 9.1 fold increase in oxygen content inside the tumor, following systemic administration of the nanodroplets. These results were also confirmed with immunofluorescence. In vivo studies showed that nanodroplets held higher rates of treatment efficacy than a clinically available benzoporphyrin derivative formulation. Histological analysis showed higher necrotic area within the tumor with perfluoropentane nanodroplets. Overall, the photoacoustic nanodroplets can significantly enhance image-guided PDT and has demonstrated substantial potential as a valid theranostic option for patient-specific photodynamic therapy-based treatments.
摘要：
光动力疗法(PDT)是众所周知的癌症疗法,其利用光来激发光敏剂并产生细胞毒性活性氧(ROS)。PDT的功效主要取决于肿瘤中的光敏剂和氧浓度。实体瘤中的缺氧促进治疗抵抗，导致不良的PDT结果。因此，需要对抗缺氧,同时向肿瘤递送足够的光敏剂用于ROS生成。在这里，我们展示了我们独特的theranoc全氟化碳纳米液滴作为氧气的三剂载体，光敏剂,和吲哚菁绿，使光触发的时空向肿瘤输送氧气。我们评估了纳米液滴的特征，并通过光声监测血氧饱和度和随后的小鼠皮下肿瘤模型中的PDT功效来验证其递送氧气的能力。用氧传感探头对成像结果进行了验证,这表明肿瘤内部的氧含量增加了9.1倍，在全身施用纳米液滴后。这些结果也用免疫荧光证实。体内研究表明,纳米液滴比临床上可用的苯并卟啉衍生物制剂保持更高的治疗效力率。组织学分析显示肿瘤内具有全氟戊烷纳米液滴的较高坏死区域。总的来说,光声纳米液滴可以显着增强图像引导的PDT，并且已显示出作为基于患者特定光动力疗法的有效治疗选择的巨大潜力。
