Cell penetrating peptides from agglutinin protein of Abrus precatorius facilitate the uptake of Imatinib mesylate

Abstract

Targeted drug delivery is of paramount importance for cancer patients. Cell penetrating peptides (CPPs) have emerged as potent vehicles for this purpose. Herein, we demonstrate CPP- like properties of two peptides: NH2-SGASDDEEIAR-COOH (SR11) and NH2-ICSSHYEPTVRIGGR-COOH (IR15), derived from the tryptic digest of Abrus precatorius agglutinin. Both IR15 and SR11 were found to be non-toxic at lower doses (up to 50μg/ml). These two peptides entered into HeLa cells through lipid raft-mediated endocytosis within 15min and penetrated the nuclear membrane in 60min of incubation. Co-treatment of peptides (20μg/ml) and Imatinib (5μM) in HeLa cells increased uptake of the drug by ∼55% and lowered the IC50 value to one-third in comparison to the drug added exclusively. However, co-treatment of TAT peptide (standard CPP) did not alter the Imatinib uptake significantly. In summary, we have identified two novel CPPs from tryptic digest of Abrus agglutinin which increased the cellular uptake of Imatinib upon co-administration. Further studies may result in deciphering a novel mode of drug delivery.