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 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.