RGD modified albumin nanospheres for tumour vasculature targeting

OBJECTIVES: Cyclic arginine-glycine-aspartic acid (RGD) peptide-anchored sterically stabilized albumin nanospheres (RGD-SN) have been investigated for the selective and preferential presentation of carrier contents at angiogenic endothelial cells overexpressing a(v) b(3) integrins on and around tumour tissue. Their targetability was assessed. METHODS: Albumin nanospheres were formulated, conjugated with RGD/RAD peptide and characterized on the basis of size and size distribution. The control Arginine-Alanine-Aspartic acid (RAD) peptide-anchored sterically stabilized nanospheres (RAD-SN) and nanosphere with 5 mol% PEG (SN) without peptide conjugate were used for comparison with RGD-SN for in vitro cell binding, in vivo organ distribution and tumor angiogenesis studies. KEY FINDINGS: The average size of all nanospheres prepared was approximately 100 nm and maximum drug entrapment was 67.2 ± 5.2%. In-vitro endothelial cell binding of nanospheres exhibited 8-fold higher binding of RGD-SN to human umbilical vein endothelial cells in comparison with the SN and RAD-SN. RGD peptide-anchored nanospheres were significantly (P ≤ 0.01) effective in the prevention of lung metastasis, angiogenesis and in effective regression of tumours compared with free fluorouracil, SN and RAD-SN. Results indicated that cyclic RGD peptide-anchored sterically stabilized nanospheres bearing fluorouracil were significantly (P ≤ 0.01) active against primary tumour and metastasis than the nontargeted sterically stabilized nanospheres and free drug. CONCLUSIONS: Cyclic RGD peptide-anchored sterically stabilized nanospheres appears promising for targeted cancer chemotherapeutics.