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 fieldof investigation in the last years. Recently, a photo-independent cytotoxic effect of(Bu3Sn)4TPPS in the blocking melanoma cell proliferation an inducing a morphology cellchange was investigated. Amphiphilic CD (ACyD) provides more water soluble andadaptable nanovectors through modulation of the balance between hydrophobic andhydrophilic chains at both CD sides. ACyD can be conveniently tailored by covalentlyappending fluorescent label or receptor-targeting glycosyl- groups and can encapsulateconventional and phototherapeutic drugs. The aim of this work was to design biomimeticnanoassemblies based on non-ionic and hydrophilic ACyD (SC6OH) for delivery of poorwater soluble organotin(IV)-porphyrin complexes in melanoma cancer cell. Nanoassemblieswere prepared by dispersion in water of (Bu3Sn)4TPPS/SC6OH organic film at 1:5 molar ratioand characterized by a combination of spectroscopic and morphological techniques. Sizedistribution, charge, drug encapsulation efficiency and in vitro release were investigated.Intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics wereevaluated by fluorescence microscopy on A375 human melanoma cells. UV-vis and emissionspectroscopy of (Bu3Sn)4TPPS/SC6OH show shifts of the peculiar bands of organotin(IV)-porphryin complex by interaction with supramolecular nanoaggregates of ACyD in aqueoussolution. Mean size was within the range 100-120 nm. ξ-potential was negative for all theformulations (–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 moreefficient internalization, a higher cytotoxic effect inducing apoptotic cell death and at lowerconcentrations a cellular morphology change blocking cell proliferation. In conclusion thestrategy of entrapping anticancer drug based on poor water-soluble porphyrin organotincomplexes in ACyD nanocarriers is here proposed as new photo-independent therapeuticapproaches against melanoma.References M.A. Costa, F. Zito, M.R. Emma, L. Pellerito, T. Fiore, C. Pellerito, G. Barbieri, Int. J. Oncol. 2011, 38,693. A. Mazzaglia, Photodynamic Tumor Therapy with Cyclodextrin Nanoassemblies. In: Cyclodextrins inPharmaceutics, Cosmetics, and Biomedicine: Current and Future Industrial Applications, E. Bilensoy(Ed.); John Wiley & Sons, Inc.: Hoboken, 2011; pp. 343-361.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2012|