Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; Division of General Thoracic Surgery, Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
Ann Thorac Surg. 2019 Jun;107(6):1613-1620. doi: 10.1016/j.athoracsur.2019.01.008. Epub 2019 Feb 8.
Nonsurgical and minimally invasive approaches for early-stage peripheral lung cancer are needed to avoid the known morbidity of surgical resection, particularly in high-risk patients. We previously demonstrated the utility of multifunctional porphyrin-phospholipid nanoparticles (porphysomes) for fluorescence imaging and phototherapy after preferential accumulation into tumors. The objective of this study was to demonstrate the feasibility of porphysome-mediated imaging and photothermal therapy using a newly developed fiberscope and thoracoscope.
To prepare this technology for clinical translation, we developed a porphysome-specific fiberscope (scanning fiber endoscope and porphysome-specific thoracoscope), both capable of detecting porphysome fluorescence, for image-guided transbronchial and transpleural photothermal therapy to treat endobronchial/peribronchial and subpleural tumors, respectively. These were tested in three animal models: human lung cancer xenografts (A549) in mice, orthotopic VX2 lung tumors in rabbits, and ex vivo pig lung into which A549 tumor tissue was transplanted.
The scanning fiber endoscope, with a 1.2-mm diameter, is small enough to pass through the working channel of a conventional bronchoscope and could visualize porphysome-laden tumors located inside or close to the peripheral bronchial wall. The porphysome-specific thoracoscope system had high sensitivity for porphysome fluorescence and enabled image-guided thoracoscopic resection of porphysome-accumulating tumors close to the pleura. Porphysomes also enhanced the efficacy of scanning fiber endoscope-guided transbronchial photothermal therapy and porphysome-specific thoracoscope-guided transpleural photothermal therapy, resulting in selective and efficient tumor tissue ablation in the rabbit and pig models.
These results support the potential for clinical translation of this novel platform to affect nonsurgical and minimally invasive treatment options for early-stage peripheral lung cancer.
需要非手术和微创方法来治疗早期周围型肺癌，以避免手术切除带来的已知发病率，特别是在高危患者中。我们之前已经证明了多功能卟啉磷脂纳米粒子（porphysomes）在优先积累到肿瘤后用于荧光成像和光疗的效用。本研究的目的是展示使用新开发的纤维镜和胸腔镜进行 porphysome 介导的成像和光热治疗的可行性。
为了将这项技术推向临床转化，我们开发了一种特定于 porphysome 的纤维镜（扫描纤维内窥镜和特定于 porphysome 的胸腔镜），两者都能够检测到 porphysome 荧光，用于图像引导经支气管和经胸膜光热治疗，分别治疗支气管内/支气管周围和胸膜下肿瘤。这些在三种动物模型中进行了测试：小鼠中的人肺癌异种移植（A549）、兔的原位 VX2 肺肿瘤和 A549 肿瘤组织移植的离体猪肺。
直径为 1.2 毫米的扫描纤维内窥镜足够小，可以通过常规支气管镜的工作通道，并可以可视化位于周围支气管壁内部或附近的载有 porphysome 的肿瘤。特定于 porphysome 的胸腔镜系统对 porphysome 荧光具有很高的灵敏度，能够在靠近胸膜的位置引导胸腔镜切除载有 porphysome 的肿瘤。卟啉还增强了扫描纤维内窥镜引导的经支气管光热治疗和特定于 porphysome 的胸腔镜引导的经胸膜光热治疗的疗效，导致兔和猪模型中的肿瘤组织选择性和有效消融。
这些结果支持将这个新平台转化为临床应用的潜力，以影响早期周围型肺癌的非手术和微创治疗选择。
