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.
Nanoassemblies based on folate-tailored amphiphilic cyclodextrin / pheophorbide complexes for targeted PDT
Giuseppe Sortino;Roberto Zagami;Antonino Mazzaglia
2016
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
