Complexes of Amphiphilic Cyclodextrins and Tributyltin(IV) derivatives as Potential nanotherapeutics against melanoma

Amphiphilic CD (ACyD) provides water soluble and adaptable nanovectors through modulation of the balance between hydrophobic and hydrophilic chains at both CD sides (Mazzaglia et al, 2011). The aim of this work was to design nanoassemblies (Scheme 1) based on non-ionic and hydrophilic ACyD (SC6OH) for delivery of poor water soluble organotin(IV)-porphyrin derivative [(Bu3Sn)4TPPS] in melanoma cancer cells (Costa et al, 2011). To characterize the porphyrin derivatives species in conditions simulating the physiological medium, a speciation with complementary techniques was carried out. In aqueous solution (<= 20 ?M) (Bu3Sn4)TPPS is present mostly as monomer as suggested by the low value of static anisotropy (?? 0.02) whilst is negligible the formation of porphyrin supramolecular aggregates. MALDI-TOF spectra show the presence of fragments (i.e. [(Bu3Sn)3TPPS]-) which are derivatives of monomeric species. Spectrofluorimetry coupled with potentiometric measurements assess in physiological conditions mainly the presence of hydrolytic species of Bu3Sn+ [(Bu3Sn)4TPPS (OH)4]4-. Nanoassemblies have been prepared by dispersion in PBS at pH= 7.4 of (Bu3Sn)4TPPS/SC6OH organic films and investigated by a combination of spectroscopic and morphological techniques. UV-Vis and emission fluorescence spectroscopy of (Bu3Sn)4TPPS/SC6OH show shifts of the peculiar bands of organotin(IV)-porphyrin derivative by interaction with ACyD supramolecular assemblies in aqueous solution. Mean size was within the range 100-120 nm. ?-potential was negative for all the formulations (-16 mV) of (Bu3Sn)4TPPS/SC6OH nanoassemblies with entrapment efficiency of about 67%. The results clearly address to the choice of amphiphilic cyclodextrin to increase the benefit on the controlled release and on protection by degradation phenomena of hydrophobic tributyltin (IV) porphyrin derivatives Intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics have been evaluated by fluorescence microscopy on A375 human melanoma cells. 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.