Nanoassemblies based on folate-tailored amphiphilic cyclodextrin / pheophorbide complexes for targeted PDT

Nowadays, active targeting of a drug in tumor sites is generally accomplished by tailoring a nanosystem with receptor targeting groups such as folate, antibodies, saccharides and peptides. Targeted PDT treatment relies on the selective accomodation of a photosensitiser (PS) in tumor sites following irradiation, thus generating the cytotoxic singlet oxygen (1O2). Here we report a nanoassembly based on amphiphilic cyclodextrin carrier (aCD, SC6OH), entrapping pheophorbide (Pheo) as PS and tailored with folate-adamantanyl (Ada-Fol) as folate receptor (FOLR1) targeting group. SC6OH@Ada-Fol /Pheo nanoassemblies (1), prepared by hydration of organic film and sonication, were studied by complementary techniques such as UV-Vis, steady-state and time-resolved fluorescence. The nanosystem 1 showed an hydrodynamic radius of about 300 nm , Z-potential of about -45 mV, Pheo loading and entrapment efficiency of about 4% and about 66%, respectively. Pheo was retained for about 2 weeks from 1 in PBS (pH=7.4) at 37°C. In order to verify the targeting properties, we evaluated in vitro the effectiveness of 1 on cell growth for different cancer cell lines over-expressing FOLR1 (MCF-7, MD-MBA and A549) and very low expressing FOLR1 (PC3). Our data indicate that the nanoassembly 1, upon redlight irradiation, inhibits cell proliferation depending on FOLR1 expression.