title: An Integrated Nanotechnology-Enabled Transbronchial Image-Guided Intervention Strategy for Peripheral Lung Cancer.
abstract: 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.
authors.affiliation: Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. Institute of Biomaterial and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. Princess Margaret Cancer Centre and TECHNA Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Cheng S
authors.initials: CS
authors.lastname: Jin
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Wada
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Takashi
authors.initials: T
authors.lastname: Anayama
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Patrick Z
authors.initials: PZ
authors.lastname: McVeigh
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Hsin Pei
authors.initials: HP
authors.lastname: Hu
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hirohashi
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.affiliation: Division of Experimental Therapeutics, Respiratory & Critical Care, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Hwang
authors.affiliation: Princess Margaret Cancer Centre and TECHNA Institute, University Health Network, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.affiliation: Graduate Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada. Institute of Biomaterial and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. Princess Margaret Cancer Centre and TECHNA Institute, University Health Network, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Kazuhiro.Yasufuku@uhn.ca gang.zheng@uhnres.utoronto.ca.
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Princess Margaret Cancer Centre and TECHNA Institute, University Health Network, Toronto, Ontario, Canada. Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. Kazuhiro.Yasufuku@uhn.ca gang.zheng@uhnres.utoronto.ca.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yasufuku
mesh_terms: D000818:Animals; D001999:Bronchoscopy; D005453:Fluorescence; D006801:Humans; D028022:Low-Level Light Therapy; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D009368:Neoplasm Transplantation; D019047:Phantoms, Imaging; D011817:Rabbits; D014183:Transplantation, Heterologous