P3.16-05 A Nanotechnology-Enabled Strategy for Image-Guided Transbronchial and Transpleural Photothermal Therapy of Peripheral Lung Cancer

Abstract

Surgical resection has been established as standard of care for early-stage peripheral non-small cell lung cancer (NSCLC). However, the development of non-surgical treatment and minimally invasive therapeutics is urgently needed due to the known morbidity of surgery, particularly in high-risk patients. We have previously demonstrated the potential of porphysome nanoparticle-enabled fluorescence-guided photothermal therapy (PTT) of peripheral lung cancer in preclinical animal models. In an effort to prepare this technology for clinical application, we developed a porphysome-specific fiberscope (scanning fiber endoscope [SFE]) and porphysome-specific thoracoscope (P-PINPOINT), both capable of operating in fluorescence mode, for image-guided transbronchial and transpleural PTT to treat endo-/peribronchial and subpleural tumors respectively. In our study, we used three animal models: an in vivo human lung cancer xenograft (A549) in mice, another in vivo orthotopic VX2 tumor in rabbits, and an ex vivo pig lung into which A549 tumor tissue was transplanted. Forty-eight hours after intravenous injection of the porphysomes, the animals were used for imaging evaluation by SFE and P-PINPOINT, followed by photothermal ablation. The SFE, whose 1.2mm diameter is small enough to pass through the working channel of a conventional bronchoscope, could visualize porphysome-laden tumors located inside or close to the peripheral bronchial wall. The P-PINPOINT system had high sensitivity for porphysome fluorescence and enabled image-guided thoracoscopic resection of porphysome-accumulated tumors close to pleural. Porphysomes also enhanced the efficacy of SFE-guided transbronchial PTT and P-PINPOINT-guided transpleural PTT, resulting in selective and efficient tumor tissue ablation in the rabbit and pig models. These promising results suggest potential in the clinical translation of this novel platform to impact non-surgical and minimally invasive treatment options for early-stage peripheral lung cancer. This could offer new strategies for the treatment of non-small cell lung cancer.