Polymeric nanospheres modified with YIGSR peptide for tumor targeting.

YIGSR peptide anchored pegylated nanospheres (YIGSR-SN) loaded with 5-fluorouracil (5-FU) were investigated for selective and preferential presentation of carrier contents at angiogenic endothelial cells over-expressing laminin receptors on and around tumor tissue and thus for assessing their targetability. Pegylated nanosphere (SN) without peptide conjugate were used for comparison. The average size of all nanosphere preparations prepared was approximately 108 nm and maximum drug entrapment was 68.5 +/- 5.2%. In vitro endothelial cell binding of nanospheres exhibited 8-fold higher binding of YIGSR-SN to HUVEC in comparison to the SN. Spontaneous lung metastasis and angiogenesis assays show that YIGSR peptide anchored nanospheres are significantly (p <or= 0.05) effective in the prevention of lung metastasis and angiogenesis compared to free 5-FU and SN. In therapeutic experiments, 5-FU, SN, and YIGSR-SN were administered intravenously on day 4 at the dose of 10 mg 5-FU/kg body weight to B16F10 tumor bearing BALB/c mice resulting in effective regression of tumors in YIGSR-SN compared with free 5-FU and SN. Results indicate that YIGSR peptide anchored pegylated nanospheres bearing 5-FU are significantly (p <or= 0.05) active against primary tumor and metastasis than the non-targeted pegylated nanospheres and free drug. Thus, YIGSR peptide anchored pegylated nanospheres hold potential of targeted cancer chemotherapeutics.