1 research outputs found
Tandem Peptide Based on Structural Modification of Poly-Arginine for Enhancing Tumor Targeting Efficiency and Therapeutic Effect
The
nonselectivity of cell penetrating peptides had greatly limited
the application in systemic administration. By conjugating a dGR motif
to the C-terminal of octa-arginine, the formed tandem peptide R8-dGR
had been proved to specifically recognize both integrin α<sub>v</sub>β<sub>3</sub> and neuropilin-1 receptors. However, the
positive charge of poly-arginine would still inevitably lead to rapid
clearance in the circulation system. Therefore, in this study, we
tried to reduce the positive charge of poly-arginine by decreasing
the number of arginine, to thus achieve improved tumor targeting efficiency.
We had designed several different R<i>x</i>-dGR peptides
(<i>x</i> = 4, 6, and 8) modified liposomes and investigated
their tumor targeting and penetrating properties both <i>in vitro</i> and <i>in vivo</i>. Among all the liposomes, R6-dGR modified
liposomes exhibited a long circulation time similar to that of PEGylated
liposomes while they retained strong penetrating ability into both
tumor cells and tumor tissues, and thus had displayed the most superior
tumor targeting efficiency. Then, paclitaxel and indocyanine green
coloaded liposomes were prepared, and R6-dGR modified coloaded liposomes
also exhibited enhanced antitumor effect on C6 xenograft tumor bearing
mice. Therefore, we suggest R6-dGR as a potential tumor targeting
ligand with both strong penetrating ability and improved pharmacokinetic
behavior, which could be further used for efficient antitumor therapy