Abstract
Glioma is a common type of primary tumor in the central nervous system. Glioma has been increasing in incidence yearly and is a serious threat to human life and health. The aim of the present study was to prepare liposomes for enhanced penetration of the blood-brain barrier and targeting of glioma. A procaine-loaded liposome modified with the cyclic pentapeptide cRGDyK (Pro/cRGDyK-L) was designed and developed. The particle size, ζ potential, encapsulation efficiency, release profile, stability and hemolysis of Pro/cRGDyK-L were characterized in vitro. The targeting and antitumor effects of Pro/cRGDyK-L were also investigated in vitro and in vivo. The results suggested that the cRGDyK peptide significantly facilitated the ability of liposomes to transfer procaine across the BBB and improved the cellular uptake of procaine by C6 glioma cells. The results further demonstrated that Pro/cRGDyK-L strongly suppressed cell motility, stimulated apoptosis and induced cell cycle arrest. The findings further confirmed that Pro/cRGDyK-L exhibited superior antitumor effects by targeting the ERK/p38MAPK pathway and thereby suppressed tumor growth in mice. In conclusion, the present study indicated the potential of Pro/cRGDyK-L as a means to provide improved therapeutic effects on glioma through the ERK/p38MAPK pathway.