The
epidermal growth factor receptor (EGFR) is a promising target for anti-
cancer therapy. The aim of this study was to design thermosensitive
liposomes (TSL), functionalized with anti-EGFR
ligands for targeted delivery and localized triggered release of
chemotherapy. For targeting, EGFR specific
peptide (GE11) and
Fab' fragments of
cetuximab were used and the effect of
ligand density on in vitro
tumor targeting was investigated.
Ligand conjugation did not significantly change the physicochemical characteristics of
liposomes. Fab'-decorated TSL (Fab'-TSL) can specifically and more efficiently bind to the EGFR overexpressed
cancer cells as compared to GE11 modified TSL.
Calcein labeled Fab'-TSL showed adequate stability at 37°C in serum (<4%
calcein released after 1h) and a temperature dependent release at above 40°C. FACS analysis and live cell imaging showed efficient and EGFR mediated cellular association as well as dramatic intracellular cargo release upon
hyperthermia. Fab'-conjugation and
hyperthermia induced enhanced
tumor cell cytotoxicity of
doxorubicin loaded TSL. The relative cytotoxicity of Fab'-TSL was also correlated to EGFR density on the
tumor cells. These results suggest that Fab'-TSL showed great potential for combinational targeted and triggered release drug delivery.