title: Real-time vascular imaging and photodynamic therapy efficacy with micelle-nanocarrier delivery of chlorin e6 to the microenvironment of melanoma.
abstract: BACKGROUND
  Strategies combining anti-vascular therapy and vascular imaging may facilitate the prediction of early response and outcome in cancer treatment.
  
  
  OBJECTIVE
  The aim of this study was to investigate the relationship between the tumor-associated vasculature in melanoma and to develop an approach for melanoma treatment by utilizing the free form and micelle form of the photosensitizer (PS) chlorin e6 in photodynamic therapy (PDT).
  
  
  METHODS
  Green fluorescence protein (GFP) expressing B16-F10 melanoma cells were implanted into the mouse ear dermis. Ce6 in free form or in micelle form was administered via the tail vein. An OV100 imaging system was used to record the red fluorescence of Ce6 to obtain real-time vascular images in the GFP tumor.
  
  
  RESULTS
  Compared to free Ce6, Ce6 linked to the micelle-nanocarrier depicted a much clearer vascular image and had an effective vascular destruction by PDT. Micelle Ce6 was localized in lysosomes and in the endoplasmic reticulum of cultured endothelial cells, implying an active endocytosis of the nano-carrier.
  
  
  CONCLUSIONS
  Micelle Ce6 can serve as a bifunctional PS for vascular imaging and PDT, which facilitates its delivery in the tumor microenvironment.
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Nursing, Min-Hwei Junior College of Health Care Management, Tainan 73658, Taiwan.
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Ping-Shan
authors.initials: PS
authors.lastname: Lai
authors.affiliation: Instrument Technology Research Center, National Applied Research Laboratories, Hsinchu 30076, Taiwan.
authors.forename: Yen-Pei
authors.initials: YP
authors.lastname: Lu
authors.affiliation: Department of Medicine and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Hsuan-Ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Pathology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung 80708, Taiwan.
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien 97002, Taiwan.
authors.forename: Rong-Kung
authors.initials: RK
authors.lastname: Tsai
authors.affiliation: Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien 97002, Taiwan.
authors.forename: Kang-Tang
authors.initials: KT
authors.lastname: Fang
authors.affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Department of Chemistry, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Chia-Yen
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung 80708, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung City 812, Taiwan.
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung 80708, Taiwan; National Environmental Health Research Center, National Health Research Institute, Miao-Li, Taiwan.
authors.forename: Hsin-Su
authors.initials: HS
authors.lastname: Yu
authors.affiliation: Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; Department of Dermatology, Kaohsiung Medical University, Chung-Ho Memorial Hospital, Kaohsiung 80708, Taiwan; Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan. Electronic address: 970457@ms.kmuh.org.tw.
authors.forename: Chung-Hsing
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Physics, National Taiwan University, Taipei 10617, Taiwan; Research Center for Applied Sciences, Academia Sinica, Taipei 11529, Taiwan. Electronic address: dptsai@phys.ntu.edu.tw.
authors.forename: Din-Ping
authors.initials: DP
authors.lastname: Tsai
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D002735:Chlorophyllides; D004337:Drug Carriers; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles; D009389:Neovascularization, Pathologic; D061848:Optical Imaging / Q000379:methods*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry; D011166:Porphyrins / Q000008:administration & dosage* / Q000737:chemistry; D012878:Skin Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D059016:Tumor Microenvironment
chemical_list: D002735:Chlorophyllides; D004337:Drug Carriers; D008823:Micelles; D017319:Photosensitizing Agents; D011166:Porphyrins; D049452:Green Fluorescent Proteins; C062985:phytochlorin
keywords: Chlorin e6; Endothelial cells; Melanoma; Micelle; Photodynamic therapy; Tumor microenvironment