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

Colloids Surf B Biointerfaces. 2016 Apr 1:140:169-175. doi: 10.1016/j.colsurfb.2015.12.042. Epub 2015 Dec 28.

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 50 μg/ml). These two peptides entered into HeLa cells through lipid raft-mediated endocytosis within 15 min and penetrated the nuclear membrane in 60 min of incubation. Co-treatment of peptides (20 μg/ml) and Imatinib (5 μM) 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.

Keywords: Abrus agglutinin; Abrus precatorius; Cell penetrating peptide; Imatinib mesylate; Imatinib mesylate (PubChem CID:123596).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abrus / chemistry*
  • Agglutinins / chemistry*
  • Amino Acid Sequence
  • Cell Line
  • Cell Survival / drug effects
  • Cell-Penetrating Peptides / administration & dosage
  • Cell-Penetrating Peptides / chemistry
  • Cell-Penetrating Peptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods
  • Drug Interactions
  • Erythrocytes / drug effects
  • HeLa Cells
  • Hemolysis / drug effects
  • Humans
  • Imatinib Mesylate / administration & dosage
  • Imatinib Mesylate / pharmacokinetics
  • Imatinib Mesylate / pharmacology*
  • Microscopy, Confocal

Substances

  • Agglutinins
  • Cell-Penetrating Peptides
  • Imatinib Mesylate