title: Micelles of zinc protoporphyrin conjugated to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer for imaging and light-induced antitumor effects in vivo.
abstract: We synthesized N-(2-hydroxypropyl)methacrylamide polymer conjugated with zinc protoporphyrin (HPMA-ZnPP) and evaluated its application for tumor detection by imaging and treatment by light exposure using in mouse sarcoma model. To characterize HPMA-ZnPP micelle, we measured its micellar size, surface charge, stability, photochemical, biochemical properties and tissue distribution. In vivo anti-tumor effect and fluorescence imaging were carried out to validate the tumor selective accumulation and therapeutic effect by inducing singlet oxygen by light exposure. HPMA-ZnPP was highly water soluble and formed micelles spontaneously having hydrophobic clustered head group of ZnPP, in aqueous solution, with a hydrodynamic diameter of 82.8±41.8 nm and zeta-potential of +1.12 mV. HPMA-ZnPP had a long plasma half-life and effectively and selectively accumulated in tumors. Although HPMA-ZnPP alone had no toxicity in S-180 tumor-bearing mice, light-irradiation significantly suppressed tumor growth in vivo, similar to the cytotoxicity to HeLa cells in vitro upon endoscopic light-irradiation. HPMA-ZnPP can visualize tumors by fluorescence after i.v. injection, which suggests that this micelle may be useful for both tumor imaging and therapy. Here we describe preparation of a new fluorescence nanoprobe that is useful for simultaneous tumor imaging and treatment, and application to fluorescence endoscopy is now at visible distance.
authors.affiliation: Research Institute for Drug Delivery System, Faculty of Pharmaceutical Science, Sojo University, Kumamoto, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Long
authors.initials: L
authors.lastname: Liao
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hitaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsukigawa
authors.forename: Vladimir
authors.initials: V
authors.lastname: Subr
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008297:Male; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D061848:Optical Imaging; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011524:Protoporphyrins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D008823:Micelles; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C017803:zinc protoporphyrin; C032976:N-(2-hydroxypropyl)methacrylamide