An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.

Early detection and efficient treatment modality of early-stage peripheral lung cancer is essential. Current nonsurgical treatments for peripheral lung cancer show critical limitations associated with various complications, requiring alternative minimally invasive therapeutics. Porphysome nanoparticle-enabled fluorescence-guided transbronchial photothermal therapy (PTT) of peripheral lung cancer was developed and demonstrated in preclinical animal models. Systemically administered porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast, as confirmed in three subtypes of orthotopic human lung cancer xenografts (A549, H460, and H520) in mice and in an orthotopic VX2 tumor in rabbits. An in-house prototype fluorescence bronchoscope demonstrated the capability of porphysomes for in vivo imaging of lung tumors in the mucosal/submucosal layers, providing real-time fluorescence guidance for transbronchial PTT. Porphysomes also enhanced the efficacy of transbronchial PTT significantly and resulted in selective and efficient tumor tissue ablation in the rabbit model. A clinically used cylindrical diffuser fiber successfully achieved tumor-specific thermal ablation, showing promising evidence for the clinical translation of this novel platform to impact upon nonsurgical treatment of early-stage peripheral lung cancer. Cancer Res; 76(19); 5870-80. ©2016 AACR.

Photothermal ablation of human lung cancer by low-power near-infrared laser and topical injection of indocyanine green.

The present study was designed to evaluate the efficacy of photothermal ablation therapy for lung cancer by low-power near-infrared laser and topical injection of indocyanine green (ICG). In vitro study 1: an 808 nm laser with 250 mW was irradiated for 10 minutes using different dilutions of ICG and the temporal thermal effect was monitored. ICG (1 mL of 0.5 g/L) was heated to a temperature of >30°C from the base temperature by laser irradiation. In vitro study 2: the cytotoxic effect of hyperthermia on human lung cancer cells was examined in different temperature and time settings. Cell viability was quantified by both an MTS assay and reculturing. Fatal conditions evaluated by reculturing were as follows: thermal treatment at 55°C for 5 minutes, 53°C for 10 minutes, and 51°C for 15 minutes. The MTS assay study suggested that thermal treatment at 59°C for 5 minutes and 57°C for 20 minutes showed a severe cytotoxic effect. In vivo study: nude mouse subcutaneous NCI-H460 human lung cancer xenograft models were used for the study. Saline or 0.5 g/L of ICG was injected topically into the tumor (n=3/group). Tumors were irradiated with a laser at 500 mW for 10 minutes. Although the tumor diameter reached 1 cm within 24 days after treatment in all 3 mice using saline/laser, tumor sizes were gradually reduced in all 3 mice using the ICG/laser. In 2 of the 3 mice using ICG/laser, tumors had disappeared macroscopically. The efficacy of the photothermal ablation therapy by low-power near-infrared laser and a topical injection of ICG was clarified using a mouse subcutaneous a lung cancer xenograft model.