Targeted Nanoclusters for Intratracheal Delivery in Intraoperative Imaging of Lung Adenocarcinoma

Lu Tang,1 Ning Li,2 Zhe Yang,3 Yangliu Lin,4 Ge Gao,5 Quan Lin,4 Yue Wang6 1Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Respiratory Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3Shandong Laboratory of Advanced Materials and Green Manufacturing at Yantai, Yanatai, Shandong, People’s Republic of China; 4State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun, Jilin, People’s Republic of China; 5Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 6Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Yue Wang, Department of Thoracic Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China, Tel/Fax +86 431-84995495, Email [email protected] Quan Lin, State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun, Jilin, People’s Republic of China, Email [email protected]: Computed tomography (CT) is widely used all over the world, and the detection rate of early lung adenocarcinoma is increasing. Minimally invasive thoracic surgery (MITS) has emerged as the preferred surgical approach for lung adenocarcinoma, but identifying small lung adenocarcinomas is difficult. Therefore, there is a need for a non-invasive, convenient and efficient way to localize lung adenocarcinomas.Materials and Methods: A targeted gold nanocluster for intraoperative fluorescence imaging by intratracheal delivery has been designed. Au-GSH-anti Napsin A nanoclusters (NapA-AuNCs) were synthesized, and their physicochemical properties and optical properties were characterized. Target effect, cytotoxicity and fluorescence time curve of NapA-AuNCs, were tested in vivo and in vitro, and intratracheal delivery was also carried.Results: NapA-AuNCs targeting lung adenocarcinoma with red fluorescence and good mucus penetration were synthesized, which had the targeting property of A549 and lung adenocarcinoma tissue, and also had very low toxicity to normal lung epithelial cells and organs. Intracheal delivery involves faster imaging of lung adenocarcinoma and less accumulation of other organs than intravenous administration.Conclusion: NapA-AuNCs targeting lung adenocarcinoma were successfully conjugated, and intratracheal delivery is a safe, effective for lung adenocarcinoma intraoperative localization.Plain Language Summary: Computed tomography (CT) is widely used all over the world, and the detection rate of early lung adenocarcinoma is increasing. But some pulmonary nodules are too small to find when surgically removing them. Therefore, there is a need for a non-invasive, convenient and efficient way to localize lung nodules. We have prepared a nanoparticle (NapA AuNCs) that can make lung adenocarcinoma emit red fluorescence. It can be intratracheal delivered into the lungs through the airway, causing lung adenocarcinoma to emit red fluorescence and remain in the body for a longer period of time. Our experiments on cells and animals have confirmed its effectiveness and low toxicity. Therefore, we believe that this targeted localization method for lung adenocarcinoma has the potential to be applied clinically. Keywords: lung adenocarcinoma, intraoperative localization, fluorescence imaging, gold nanoparticles, intratracheal delivery, Napsin A