title: Cancer phototherapy via selective photoinactivation of respiratory chain oxidase to trigger a fatal superoxide anion burst.
abstract: OBJECTIVE
  Here, we develop a novel cancer treatment modality using mitochondria-targeting, high-fluence, low-power laser irradiation (HF-LPLI) in mouse tumor models and explore the mechanism of mitochondrial injury by HF-LPLI.
  
  
  RESULTS
  We demonstrated that the initial reaction after photon absorption was photosensitization of cytochrome c oxidase (COX), to inhibit enzymatic activity of COX in situ and cause respiratory chain superoxide anion (O2(-•)) burst. We also found that HF-LPLI exerted its main tumor killing effect through mitochondrial O2(-•) burst via electron transport chain (ETC). These phenomena were completely absent in the respiration-deficient cells and COX knockdown cells. With a carefully selected irradiation protocol, HF-LPLI could efficaciously destroy tumors. The inhibition of enzymatic activity of COX and generation of O2(-•) by HF-LPLI in vivo were also detected.
  
  
  METHODS
  It is the first time that the mechanism involved in the interaction between light and its photoacceptor under HF-LPLI treatment is clarified. Our results clearly indicate that HF-LPLI initiates its effects via targeted COX photoinactivation and that the tumor-killing efficacy is dependent of the subsequent mitochondrial O2(-•) burst via ETC.
  
  
  CONCLUSIONS
  Based on both in vitro and in vivo results, we conclude that HF-LPLI can selectively photoinactivate respiratory chain oxidase to trigger a fatal mitochondrial O2(-•) burst, producing oxidative damage on cancer cells. This study opens up the possibilities of applications of HF-LPLI as a mitochondria-targeting cancer phototherapy.
authors.affiliation: 1 MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou, China .
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wu
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhou
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Wei
authors.forename: Wei R
authors.initials: WR
authors.lastname: Chen
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004579:Electron Transport / Q000528:radiation effects; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D006801:Humans; D028022:Low-Level Light Therapy; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000201:enzymology / Q000528:radiation effects; D009368:Neoplasm Transplantation; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; D003576:Electron Transport Complex IV