Hideki Ujiie1, Lili Ding2, Rong Fan2, Tatsuya Kato1, Daiyoon Lee1, Kosuke Fujino1, Tomonari Kinoshita1, Chang Young Lee1, Thomas K Waddell1, Shaf Keshavjee1, Brian C Wilson3, Gang Zheng4, Juan Chen2, Kazuhiro Yasufuku5. 1. Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario. 2. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario. 3. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario; Department of Medical Biophysics, University of Toronto, Toronto, Ontario. 4. Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario; Department of Medical Biophysics, University of Toronto, Toronto, Ontario; Guided Therapeutics, Princess Margaret Cancer Centre and TECHNA Institute, University Health Network, Toronto, Ontario; Institute of Biomaterial and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. 5. Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, Ontario; Department of Medical Biophysics, University of Toronto, Toronto, Ontario; Guided Therapeutics, Princess Margaret Cancer Centre and TECHNA Institute, University Health Network, Toronto, Ontario; Institute of Biomaterial and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. Electronic address: kazuhiro.yasufuku@uhn.ca.
Abstract
BACKGROUND: We have developed ultrasmall porphyrin-high-density lipoprotein (HDL) nanoparticles (<20 nm), called "porphyrinHDL," that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become fluorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted to scavenger receptor class B type I (SR-BI) expressed on lung cancer cells as a first step toward development of a minimally invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. METHODS: The in vitro uptake of porphyrinHDL and the corresponding PDT efficacy were evaluated in both SR-BI-positive and SR-BI-negative lung cancer cell lines. A clinically relevant orthotopic lung cancer model in mice was used to examine fluorescence activation and quantification of uptake in tumor. In addition, we investigated the effect of porphyrinHDL-mediated PDT. RESULTS: PorphyrinHDL promoted proper intracellular uptake in the H460 human lung cancer cell line. When irradiated with a 671-nm PDT laser, porphyrinHDL produced significant therapeutic effectiveness in vitro. After systemic administration in mice with orthotopic lung cancer xenografts, porphyrinHDL demonstrated selective accumulation and photoactivation in tumor with significantly enhanced disease-to-normal tissue contrast. Moreover, porphyrinHDL-PDT significantly induced cell apoptosis in lung tumors (73.2%) without toxicity in normal tissues or damage to adjacent critical structures. CONCLUSIONS: SR-BI-targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.
BACKGROUND: We have developed ultrasmall porphyrin-high-density lipoprotein (HDL) nanoparticles (<20 nm), called "porphyrinHDL," that have a high density of porphyrin molecules and dissociate rapidly upon tumor cell accumulation to become fluorescent and photoactive. This is introduced as a novel activatable photosensitizer for image-guided photodynamic therapy (PDT). Here, we report the studies of these nanoparticles targeted to scavenger receptor class B type I (SR-BI) expressed on lung cancer cells as a first step toward development of a minimally invasive treatment for peripheral lung cancer and metastatic lymph nodes of advanced lung cancer. METHODS: The in vitro uptake of porphyrinHDL and the corresponding PDT efficacy were evaluated in both SR-BI-positive and SR-BI-negative lung cancer cell lines. A clinically relevant orthotopic lung cancer model in mice was used to examine fluorescence activation and quantification of uptake in tumor. In addition, we investigated the effect of porphyrinHDL-mediated PDT. RESULTS:PorphyrinHDL promoted proper intracellular uptake in the H460 humanlung cancer cell line. When irradiated with a 671-nm PDT laser, porphyrinHDL produced significant therapeutic effectiveness in vitro. After systemic administration in mice with orthotopic lung cancer xenografts, porphyrinHDL demonstrated selective accumulation and photoactivation in tumor with significantly enhanced disease-to-normal tissue contrast. Moreover, porphyrinHDL-PDT significantly induced cell apoptosis in lung tumors (73.2%) without toxicity in normal tissues or damage to adjacent critical structures. CONCLUSIONS:SR-BI-targeted porphyrinHDL-mediated PDT of lung cancer is selective and effective in vitro and in vivo. These initial proof-of-principle studies suggest the potential of a "smart" PDT approach for highly selective tumor ablation.
Authors: Samuel C Delk; Arnab Chattopadhyay; Joan Carles Escola-Gil; Alan M Fogelman; Srinivasa T Reddy Journal: Semin Cancer Biol Date: 2020-11-11 Impact factor: 17.012