Chronic myeloid leukemia is a stem cell disease with the presence of 
Philadelphia chromosome generated through reciprocal translocation of chromosome 
9 and 22. The use of first- and second-generation tyrosine kinase inhibitors has 
been successful to an extent. However, resistance against such drugs is an 
emerging problem. Apart from several drug-resistant mechanisms, drug 
influx/efflux ratio appears to be one of the key determinants of therapeutic 
outcomes. In addition, intracellular accumulation of drug critically depends on 
cell membrane fluidity and lipid raft dynamics. Previously, we reported two 
novel cell-penetrating peptides (CPPs), namely, cationic IR15 and anionic SR11 
present in tryptic digest of Abrus agglutinin. Here, the potential of IR15 and 
SR11 to influence intracellular concentration of imatinib has been evaluated. 
Fluorescent correlation spectroscopy and lifetime imaging were employed to map 
membrane fluidity and lipid raft distribution following peptide-drug 
co-administration. Results show that IR15 and SR11 are the two CPPs which can 
modulate membrane fluidity and lipid raft distribution in K562 cells. Both IR15 
and SR11 significantly reduce the viability of CML cells in the presence of 
imatinib by increasing the intracellular accumulation of the drug.