title: Photochemical internalization of tamoxifens transported by a "Trojan-horse" nanoconjugate into breast-cancer cell lines.
abstract: Photochemical internalization (PCI) has shown great promise as a therapeutic alternative for targeted drug delivery by light-harnessed activation. However, it has only been applicable to therapeutic macromolecules or medium-sized molecules. Herein we describe the use of an amphiphilic, water-soluble porphyrin-β-cyclodextrin conjugate (mTHPP-βCD) as a "Trojan horse" to facilitate the endocytosis of CD-guest tamoxifens into breast-cancer cells. Upon irradiation, the porphyrin core of mTHPP-βCD expedited endosomal membrane rupture and tamoxifen release into the cytosol, as documented by confocal microscopy. The sustained complexation of mTHPP-βCD with tamoxifen was corroborated by 2D NMR spectroscopy and FRET studies. Following the application of PCI protocols with 4-hydroxytamoxifen (4-OHT), estrogen-receptor β-positive (Erβ+, but not ERβ-) cell groups exhibited extensive cytotoxicity and/or growth suspension even at 72 h after irradiation.
authors: Department of Radiation Biology (T.A.T., K.B.) and Department of Biochemistry (E.S.), Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo (Norway). Theodossis.Theodossiou@rr-research.no.
authors: Theodossis A
authors: TA
authors: Theodossiou
authors: A Ricardo
authors: AR
authors: Gonçalves
authors: Konstantina
authors: K
authors: Yannakopoulou
authors: Ellen
authors: E
authors: Skarpen
authors: Kristian
authors: K
authors: Berg
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008027:Light; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D058726:Nanoconjugates / Q000737:chemistry*; D011166:Porphyrins / Q000737:chemistry; D013629:Tamoxifen / Q000737:chemistry* / Q000633:toxicity; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D058726:Nanoconjugates; D011166:Porphyrins; D047392:beta-Cyclodextrins; C437342:tetra(3-hydroxyphenyl)porphine; D013629:Tamoxifen; C031215:betadex
keywords: antitumor agents; cyclodextrins; drug delivery; photochemical internalization; porphyrinoids