FOLATE-TAILORED AMPHIPHILIC CYCLODEXTRINS AS CARRIERS OF PHEOPHORBIDE FOR TARGETED PDT

One of the most used strategies to achieve drug active targeting on solid tumours relies on the functionalization of carrier system with folate group as ligand for the folate receptor (FR-α). Targeted PDT treatment implies selective accommodation of a photosensitiser (PS) in tumour sites and the subsequent irradiation generates the cytotoxic singlet oxygen (1O2). Here we report nanoassemblies based on amphiphilic cyclodextrin carrier (aCD, SC6OH),1,2 entrapping pheophorbide (Pheo) as PS and tailored with folate–adamantanyl (Ada-Fol). ROESY on SC6OH/Ada-Fol points out the exposition of Fol outside the amphiphile and the strong interaction of Ada with CD cavity. SC6OH@Ada-Fol/Pheo nanoassemblies were investigated by complementary techniques such as UV-Vis, steady-state fluorescence and characterized to elucidate size, drug loading and to get insight on the PS aggregation behaviour. The nanosystem showed an hydrodynamic radius of 300 nm, Z-potential of -50 mV, Pheo loading and entrapment efficiency of 5% and 86%, respectively. Pheo was retained for 2 weeks in PBS (pH=7.4) at 37°C. In order to verify the targeting properties, we evaluated in vitro the effectiveness of nanoasseblies on cell growth in cell lines expressing different levels of FR-α (MCF-7 cells high expression; PC3 cells low expression). Our data indicate that the nanoassembly, upon red-light irradiation, inhibits cell proliferation depending on FR-α expression.