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: Theodossis A Theodossiou, A Ricardo Gonçalves, Konstantina Yannakopoulou, Ellen Skarpen, Kristian Berg
• Journal: Angewandte Chemie (International ed. in English) (Angew Chem Int Ed Engl) Vol. 54 Issue 16 Pg. 4885-9 (Apr 13 2015) ISSN: 1521-3773 [Electronic] Germany
• PMID: 25663536 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

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

Topics

• 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, toxicity)
• beta-Cyclodextrins (chemistry)