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-ß-cyclodextrin conjugate (mTHPP-ßCD) as a "Trojan horse" to facilitate the endocytosis of CD-guest tamoxifens into breast-cancer cells. Upon irradiation, the porphyrin core of mTHPP-ßCD expedited endosomal membrane rupture and tamoxifen release into the cytosol, as documented by confocal microscopy. The sustained complexation of mTHPP-ßCD with tamoxifen was corroborated by 2D NMR spectroscopy and FRET studies. Following the application of PCI protocols with 4-hydroxytamoxifen (4-OHT), estrogen-receptor ß-positive (Erß+, but not ERß-) cell groups exhibited extensive cytotoxicity and/or growth suspension even at 72 h after irradiation.

A multifunctional bichromophoric nanoaggregate for fluorescence imaging and simultaneous photogeneration of RNOS and ROS.

We report the design, preparation, and properties of a nanoaggregate formed in phosphate buffer solution by a porphyrin-ß-cyclodextrin (ß-CD) conjugate and a nitric oxide photodonor tailored to fit the ß-CD cavity. The small nanoassembly with a diameter of about 13 nm exhibits the typical red fluorescence of the porphyrin chromophore. The empty cavity of the ß-CD unit in the nanoaggregate is able to accommodate the NO photodonor, thereby forming a supramolecular bichromophoric aggregate with diameter of about 16 nm. This nanoconstruct preserves the fluorescence of the porphyrin core and is able to generate nitric oxide and singlet oxygen under illumination with visible light. The nanoassembly internalizes in melanoma cells, can be mapped therein by fluorescence microscopy, and induces a significant level of cell mortality, probably due to the combined action of reactive nitrogen oxide species (RNOS) and reactive oxygen species (ROS).