Proteolytically Stable Cyclic Decapeptide for Breast Cancer Cell Targeting

Starting
with a previously reported linear breast cancer targeting
decapeptide WxEAAYQkFL, here we report the synthesis of a novel cyclic
peptide analogue cyclic WXEAAYQkFL. The N- to C-terminus amide cyclized
peptide with one d-amino acid (k) displayed higher uptake
by breast cancer cells, with minimal uptake by the noncancerous cells
compared to the linear peptide with two d-amino acids (x
and k), and was stable toward proteolytic degradation. When immobilized
on gold microcantilever surface, the cyclic peptide was able to capture
breast cancer cells specifically and sense samples with ≥25
cancer cells/mL. Animal studies using mice carrying orthotopic breast
MDA-MB-231 tumors showed that the cyclic peptide preferentially accumulates
in tumor (2 h after injection) and is rapidly cleared from all other
organs except kidneys and liver. The study highlights the discovery
of a novel proteolytically stable cyclic peptide that can be used
for targeted drug delivery or for enumerating circulating breast tumor
cells.