Photochemical Internalization of Tamoxifens Transported by a "Trojan-Horse" Nanoconjugate into Breast-Cancer Cell Lines
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...
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| Published in: | Angewandte Chemie International Edition Vol. 54; no. 16; pp. 4885 - 4889 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Weinheim
WILEY-VCH Verlag
13-04-2015
WILEY‐VCH Verlag Wiley Subscription Services, Inc |
| Edition: | International ed. in English |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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.
Smuggled within enemy walls: A porphyrin–β‐cyclodextrin (mTHPP–βCD) conjugate was used to “smuggle” small tamoxifen (TAM) molecules into cells by endocytosis on the command of light (see picture; FITC=fluorescein isothiocyanate). Upon irradiation with red light, the porphyrin ruptured the endosomal membranes, and the large tamoxifen payload that was released caused substantial and permanent cytotoxicity to tamoxifen‐sensitive MCF7 cells. |
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| Bibliography: | ArticleID:ANIE201500183 K.B. and T.A.T. gratefully acknowledge the European Community for financially supporting this research through the Marie Curie Intra-European Fellowship HYPERTAM (327075). K.Y. and A.R.G. thank the Marie Curie Program No. 237962 CYCLON (FP7-PEOPLE-ITN-2008) for financial support to MC fellow A.R.G. and funding of the research. Moreover, A.R.G. is indebted to Assoc. Prof. Helena Cabral-Marques, Faculty of Pharmacy, University of Lisbon, for helpful discussions and support. Finally, we thank Seahorse Biosciences for the kind loan of a Seahorse XFe96 Analyzer, which made the metabolic studies possible. ark:/67375/WNG-NVVVFXH4-G European Community istex:2C1D78C5240FAC85021E48681E86BF042294C622 K.B. and T.A.T. gratefully acknowledge the European Community for financially supporting this research through the Marie Curie Intra‐European Fellowship HYPERTAM (327075). K.Y. and A.R.G. thank the Marie Curie Program No. 237962 CYCLON (FP7‐PEOPLE‐ITN‐2008) for financial support to MC fellow A.R.G. and funding of the research. Moreover, A.R.G. is indebted to Assoc. Prof. Helena Cabral‐Marques, Faculty of Pharmacy, University of Lisbon, for helpful discussions and support. Finally, we thank Seahorse Biosciences for the kind loan of a Seahorse XFe96 Analyzer, which made the metabolic studies possible. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 1433-7851 1521-3773 |
| DOI: | 10.1002/anie.201500183 |