title: Coating lanthanide nanoparticles with carbohydrate ligands elicits affinity for HeLa and RAW264.7 cells, enhancing their photodamaging effect.
abstract: Lanthanide nanoparticles (LNPs) conjugated with monosaccharides were synthesized as a photon energy-upconverting nanodevice with affinity to cancer cells. The conjugates were designed to selectively damage the cancer cells containing protoporphyrin IX, a photosensitizer endogenously synthesized from priorly administrated 5-aminolevlunic acid (ALA), by a highly tissue-penetrative near-infrared (NIR) irradiation. First of all, the affinities of monosaccharides toward cells (HeLa, RAW264.7, and MKN45) were assessed by a novel cell aggregation assay with trivalent monosaccharide-citric acid conjugates. As a result, HeLa exhibited high affinity for glucose, while RAW264.7 for glucose, galactose, mannose, and fucose. A similar cell-monosaccharide affinity was microscopically observed when the cells were mixed with monosaccharide-LNP conjugates and rinsed, in which the high affinity LNP probes luminesced on the cells. The high affinity monosaccharide-LNPs showed greater photodamaging effects than the unmodified LNP toward the corresponding cells, when the cells were pretreated with ALA and irradiated by NIR. This study demonstrates that carbohydrates can be used as selective ligands for cancer cells in a photodynamic therapy with LNP.
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanamori
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sawamura
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Sotokawa
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Mori
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Inada
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ohkubo
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Shun-Ichiro
authors.initials: SI
authors.lastname: Ogura
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Murayama
authors.affiliation: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
authors.forename: Eigo
authors.initials: E
authors.lastname: Otsuji
authors.affiliation: School of Life Science and Technology, Tokyo Institute of Technology, J2-10, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. Electronic address: hyuasa@bio.titech.ac.jp.
authors.forename: Hideya
authors.initials: H
authors.lastname: Yuasa
mesh_terms: D000818:Animals; D002241:Carbohydrates / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D028581:Lanthanoid Series Elements / Q000737:chemistry / Q000494:pharmacology*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D013329:Structure-Activity Relationship
chemical_list: D002241:Carbohydrates; D028581:Lanthanoid Series Elements; D009942:Organometallic Compounds; D017319:Photosensitizing Agents
keywords: 5-Aminolevlunic acid (ALA); Lanthanide nanoparticles (LNPs); Monosaccharides; Photodynamic therapy (PDT); Protoporphyrin IX (PPIX)