Photochemical internalization of tamoxifens transported by a "Trojan-horse" nanoconjugate into breast-cancer cell lines

Angew Chem Int Ed Engl. 2015 Apr 13;54(16):4885-9. doi: 10.1002/anie.201500183. Epub 2015 Feb 6.

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.

Keywords: antitumor agents; cyclodextrins; drug delivery; photochemical internalization; porphyrinoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Carriers / chemistry*
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Light
  • MCF-7 Cells
  • Magnetic Resonance Spectroscopy
  • Microscopy, Confocal
  • Nanoconjugates / chemistry*
  • Porphyrins / chemistry
  • Tamoxifen / chemistry*
  • Tamoxifen / toxicity
  • beta-Cyclodextrins / chemistry

Substances

  • Drug Carriers
  • Nanoconjugates
  • Porphyrins
  • beta-Cyclodextrins
  • tetra(3-hydroxyphenyl)porphine
  • Tamoxifen
  • betadex