To enhance the anticancer activity, tumor penetration ability of the hybrid anticancer peptide, in this study, a TAT (RKKRRQRRR) peptide modified kla peptide (KLAKLAKKLAKLAK, with all D-amino acids), named kla-TAT, was co-administrated with the homing/penetrating peptide iRGD which could enhance the permeability of chemical drug in solid tumor and tumor vessel by co-administration. In this study, the nonsmall cell lung cancer A549 cell line with the iRGD targeting receptor neuropilin-1 high expression was selected to establish the 2D monolayer cell, 3D multiple cell spheroids, and xenograft mice model. The co-administration of iRGD strengthened the permeability of kla-TAT peptide against A549 2D and 3D sphere model with the penetration improvement property of iRGD; more importantly, co-administration with iRGD dramatically enhanced the accumulation of kla-TAT peptide in tumor tissue on the xenograft mice model with the homing property of iRGD. The co-administration of iRGD strategy confers targeting ability to the hybrid peptide kla-TAT. We believe the chemical conjugation plus co-administration approach may provide a promising way for cancer treatment in clinical practices.
Keywords: accumulation; co-administration; iRGD; kla-TAT; permeability.
© 2018 John Wiley & Sons A/S.