title: Access to a novel near-infrared photodynamic therapy through the combined use of 5-aminolevulinic acid and lanthanide nanoparticles.
abstract: BACKGROUND
  There have been considerable efforts to develop photodynamic therapy (PDT) for cancer, in which photoirradiation of a sensitizer delivered near cancer cells results in the conversion of oxygen into active species, causing cell destruction. Aiming at the best cancer selectivity, one PDT method employed protoporphyrin IX (PPIX), which selectively accumulated in cancer cells after oral administration of 5-aminolevulinic acid (ALA). The drawback, however, is that blue incident lights are required to excite PPIX, resulting in low tissue penetrability, and therefore limiting its application to surface cancers.
  
  
  METHODS
  To overcome the low penetrability of the incident light, we employed a light energy upconverter, lanthanide nanoparticle (LNP), which, upon irradiation with highly penetrative near-infrared (NIR) radiation, emits visible light within the Q-band region of PPIX absorbance allowing its sensitization. To discover the optimum conditions for the LNP-assisted PDT, the cytotoxicity and PPIX-sensitizability of LNPs were first studied. Then, the LNP-assisted PDT was validated using the MKN45 cell line: cells were pretreated with ALA and LNP, irradiated with a 975-nm diode laser, and subjected to MTT assay to measure cell viability.
  
  
  RESULTS
  The singlet oxygen generation on NIR-irradiation of the PPIX-LNP mixture was proved, indicating that the emission from LNP could excite the PPIX sensitizer. An intermittent NIR-irradiation for 32 min of MKN45, pretreated with LNP (1mg/mL) and ALA (2mM), caused 87% cell destruction.
  
  
  CONCLUSIONS
  The potential applicability of the NIR-irradiation PDT with ALA- and LNP-pretreated cancer cells was demonstrated.
authors.affiliation: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimoyama
authors.forename: Hiroya
authors.initials: H
authors.lastname: Watase
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Ogura
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Hagiya
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Takahashi
authors.forename: Katsushi
authors.initials: K
authors.lastname: Inoue
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Murayama
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohkubo
authors.forename: Hideya
authors.initials: H
authors.lastname: Yuasa
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004359:Drug Therapy, Combination; D006801:Humans; D007259:Infrared Rays / Q000627:therapeutic use; D028581:Lanthanoid Series Elements / Q000008:administration & dosage*; D053758:Nanoparticles / Q000008:administration & dosage*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D028581:Lanthanoid Series Elements; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid
keywords: 5-Aminolevulinic acid; Lanthanide nanoparticle; Near-infrared; Photodynamic therapy; Up-conversion luminescence