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Nanoparticle targeted folate receptor 1-enhanced photodynamic therapy for lung cancer

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Title: Nanoparticle targeted folate receptor 1-enhanced photodynamic therapy for lung cancer
Other Titles: Folate receptor targeted PDT in lung cancer
Authors: Kato, Tatsuya Browse this author
Jin, Cheng S. Browse this author
Ujiie, Hideki Browse this author
Lee, Daiyoon Browse this author
Fujino, Kosuke Browse this author
Wada, Hironobu Browse this author
Hu, Hsin-pei Browse this author
Weersink, Robert A. Browse this author
Chen, Juan Browse this author
Kaji, Mitsuhito Browse this author
Kaga, Kichizo Browse this author →KAKEN DB
Matsui, Yoshiro Browse this author →KAKEN DB
Wilson, Brian C. Browse this author
Zheng, Gang Browse this author
Yasufuku, Kazuhiro Browse this author
Keywords: photodynamic therapy (PDT)
lung cancer
folate receptor 1 (FOLR1)
Issue Date: Nov-2017
Publisher: Elsevier
Journal Title: Lung Cancer
Volume: 113
Start Page: 59
End Page: 68
Publisher DOI: 10.1016/j.lungcan.2017.09.002
PMID: 29110850
Abstract: Objective: Despite modest improvements, the prognosis of lung cancer patients has still remained poor and new treatment are urgently needed. Photodynamic therapy (PDT), the use of light-activated compounds (photosensitizers) is a treatment option but its use has been restricted to central airway lesions. Here, we report the use of novel porphyrin-lipid nanoparticles (porphysomes) targeted to folate receptor 1 (FOLR1) to enhance the efficacy and specificity of PDT that may translate into a minimally-invasive intervention for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. Materials and methods: The frequency of FOLR1 expression in primary lung cancer and metastatic lymph nodes was first analyzed by human tissue samples from surgery and endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA). Confocal fluorescence microscopy was then used to confirm the cellular uptake and fluorescence activation in lung cancer cells, and the photocytotoxicity was evaluated using a cell viability assay. In vivo fluorescence activation and quantification of uptake were investigated in mouse lung orthotopic tumor models, followed by the evaluation of in vivo PDT efficacy. Results: FOLR1 was highly expressed in metastatic lymph node samples from patients with advanced lung cancer and was mainly expressed in lung adenocarcinomas in primary lung cancer. Expression of FOLR1 in lung cancer cell lines corresponded with the intracellular uptake of folate-porphysomes in vitro. When irradiated with a 671 nm laser at a dose of 10 J/cm2, folate-porphysomes showed marked therapeutic efficacy compared with untargeted porphysomes (28% vs. 83% and 24% vs. 99% cell viability in A549 and SBC5 lung cancer cells, respectively). Systemically-administered folate-porphysomes accumulated in lung tumors with significantly enhanced disease-to-normal tissue contrast. Folate-porphysomes mediated PDT successfully inhibited tumor cell proliferation and activated tumor cell apoptosis. Conclusion: Folate-porphysome based PDT shows promise in selectively ablating lung cancer based on FOLR1 expression in these preclinical models.
Rights: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
Type: article (author version)
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 加藤 達哉

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