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Porphysome nanoparticle-enabled minimally invasive transbronchial photothermal ablation of lung cancer

Gang Zheng

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Canadian Institutes of Health Research (CIHR)
Lung cancer is responsible for 28% of all cancer deaths, more than breast, prostate and colon combined. Given the substantial mortality benefits with early detection, there will be more patients diagnosed with early-stage disease. Surgery is the standard care for these patients, but approximately 25% are medically inoperable, thus requiring effective alternative treatment. Image-guided laser thermal ablation via optical fiber delivery is one of the most promising non-surgical options. However, its clinical use has two major limitations: 1) the current method of light delivery placing the optical fiber into the tumor through the skin risks serious complications, and 2) very high light doses are needed to completely eradicate tumors due to the low preferential light absorption by the tumor tissue, so that there is risk to adjacent normal tissues. We propose to address both limitations using a novel platform that combines unique technologies developed by our multidisciplinary translational team. The first element is the use of innovative image-guided transbronchial light delivery, based on clinically-proven methods pioneered by Dr Yasufuku. This allows fiber placement/light irradiation to be done "from the inside" using an ultra-thin bronchoscopic approach, and will resolve the first safety issue. Secondly, Dr Zheng's lab recently discovered all-organic, nontoxic nanoparticles ("porphysomes") that will absorb the light energy with high efficiency, and thereby restrict the thermal damage to the tumor target. These nanoparticles can be actively or passively targeted to the tumor. Finally, photothermal treatment planning, light delivery and dosimetry have been developed by Dr Wilson and applied clinically in localized prostate cancer. Successful integration and validation in preclinical animal models of these world-leading technologies has potential to be rapidly translated into a novel, curative and very safe treatment modality for early-stage lung cancer patients.

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