Porphyrin tributyltin(IV) complexes for a novel approach in the tratment of human melanoma

Abstract

Melanoma is the most deadly form of skin cancer, largely refractory to existing therapies. The study of porphyrin derivatives as potential anti-tumor drugs has been an interesting field of investigation in the last years. Recently, a photo-independent cytotoxic effect of (Bu3Sn)4TPPS in the blocking melanoma cell proliferation an inducing a morphology cell change was investigated.[1] Amphiphilic CD (ACyD) provides more water soluble and adaptable nanovectors through modulation of the balance between hydrophobic and hydrophilic chains at both CD sides. ACyD can be conveniently tailored by covalently appending fluorescent label or receptor-targeting glycosyl- groups and can encapsulate conventional and phototherapeutic drugs.[2] The aim of this work was to design biomimetic nanoassemblies based on non-ionic and hydrophilic ACyD (SC6OH) for delivery of poor water soluble organotin(IV)-porphyrin complexes in melanoma cancer cell. Nanoassemblies were prepared by dispersion in water of (Bu3Sn)4TPPS/SC6OH organic film at 1:5 molar ratio and characterized by a combination of spectroscopic and morphological techniques. Size distribution, charge, drug encapsulation efficiency and in vitro release were investigated. Intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics were evaluated by fluorescence microscopy on A375 human melanoma cells. UV-vis and emission spectroscopy of (Bu3Sn)4TPPS/SC6OH show shifts of the peculiar bands of organotin(IV)- porphryin complex by interaction with supramolecular nanoaggregates of ACyD in aqueous solution. Mean size was within the range 100-120 nm. ξ-potential was negative for all the formulations (–16 mV in (Bu3Sn)4TPPS/SC16OH system with loading capacity of 18%). Delivering of (Bu3Sn)4TPPS by ACyD with respect to free (Bu3Sn)4TPPS provoke a more efficient internalization, a higher cytotoxic effect inducing apoptotic cell death and at lower concentrations a cellular morphology change blocking cell proliferation. In conclusion the strategy of entrapping anticancer drug based on poor water-soluble porphyrin organotin complexes in ACyD nanocarriers is here proposed as new photo-independent therapeutic approaches against melanoma. References [1] M.A. Costa, F. Zito, M.R. Emma, L. Pellerito, T. Fiore, C. Pellerito, G. Barbieri, Int. J. Oncol. 2011, 38, 693. [2] A. Mazzaglia, Photodynamic Tumor Therapy with Cyclodextrin Nanoassemblies. In: Cyclodextrins in Pharmaceutics, Cosmetics, and Biomedicine: Current and Future Industrial Applications, E. Bilensoy (Ed.); John Wiley & Sons, Inc.: Hoboken, 2011; pp. 343-361.