Nanoassemblies of amphiphilic cyclodextrin and tributyltin(IV) complexes of meso-tetra (4-sulfonatophenyl)porphine: spectroscopy, release and cytotoxicity on human melanoma cells.

The study of porphirin derivatives as potential anti-tumour drugs has been an interesting field of investigation in the last years. Melanoma, a solid tumour that arises from pigment producing melanocytes, is the most aggressive and lethal type form of cutaneous cancer and its incidence is increasing more rapidly than any other tumours. Recently, the cytotoxic effects of diorganotin(IV) and triorganotin(IV)-meso-tetra(4-sulfonatophenyl)porphirine derivatives (R2Sn)2TPPS and (R3Sn)4TPPS (R= Me, Bu) were tested and (Bu2Sn)2TPPS and (Bu3Sn)4TPPS showed cytotoxicity on A375 human melanoma cells [1]. In particular (Bu3Sn)4TPPS besides blocking melanoma cell proliferation induced a morphology cell change [2]. However, its low solubility in water could give a very low bioavailability. Supramolecular aggregates of amphiphilic cyclodextrins (ACyD) are versatile systems toward the encapsulation of both hydrophobic and hydrophilic guests and are widely used to increase bioavailability of poorly water soluble drugs. ACyD can form in aqueous solution micelles, vesicles and generally nanoparticles according to the balance between hydrophobic and hydrophilic chain linked to the both CD sides. ACyD can be modified with receptor targeting groups to direct selectively the drug to the site of action. Photosensitiser drugs embedded in cationic CD nanoassemblies were effective in inducing photodynamic damage in cancer cells [3]. In this contribute we report the entrapment process between poor water soluble tributyltin(IV)-meso-tetra(4-sulfonatophenyl)porphine derivative and non-ionic amphiphilic cyclodextrin (heptakis(2-O-oligo- (ethylene oxide)-6-alkylthio)-?-CD . The occurrence of various species at different porphyrin:ACyD ratios were studied by a combination of UV/Vis absorption, state-stationary fluorescence, fluorescence anisotropy. The systems were characterized for size distribution, charge, drug encapsulation efficiency and in vitro release. The cytotoxic effect of the (Bu3Sn)4TPPS/ACyD nanoassemblies was finally evaluated on A375 human melanoma cells. REFERENCES 1. Costa, M. A.; Pellerito, L.; Izzo, V.; Fiore, T.; Pellerito, C.; Melis, M.; Musmeci, M. T.; Barbieri, G. Cancer Letters, 2006, 238, 284-294. 2. Costa, M.A.; Gulino L.; Pellerito L.; Fiore T.; Pellerito C.; Barbieri G.; Oncology Reports, 2009, 21, 593-599 3. Sortino S., Mazzaglia, A., Monsù Scolaro, L., Marino Merlo, F., Valveri, V., Sciortino, M. T. Biomaterials, 2006, 27, 4256-4265.