cRGDyK‑modified procaine liposome inhibits the proliferation and motility of glioma cells via the ERK/p38MAPK pathway

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.

Liposomal Nanomaterials: A Rising Star in Glioma Treatment

“…Liposomes have the advantages of protecting drugs from enzyme degradation, nonimmunogenicity, low toxicity, high biocompatibility, flexibility, and biodegradability. 90 Most liposomes have a hydrophilic core with hydrophobic phospholipid bilayer structure, which can wrap hydrophilic or hydrophobic drugs, or both. Therefore, liposomal drug delivery systems can increase the solubility of hydrophobic drugs and protect them from metabolism in body fluids.…”

“… 36 Another form of RGD peptide (cRGDyK) significantly promoted the transport of procaine in liposomes across the BBB and improved procaine uptake by rat C6 glioma cells. 90 Mannose sulfonate liposomes have also been developed for the targeted delivery of chlorogenic acid (CHA) to tumor-associated macrophages (TAMs). The prepared CHA-mannose sulfonate liposomes had an ideal particle size, good stability, and preferential accumulation in tumors through mannose receptor-mediated targeting.…”

“… [ 132 ] Peptide cRGDyK‑cholesterol Procaine C6 114.23±6.1 Superior antitumor effects. [ 90 ] GRP78 MTI-31 U87 MG 122.2±1.83 Significant improvement in the median survival time. [ 133 ] Cabazitaxel U87 MG 140 Higher drug accumulation, barriers crossing capability.…”

Cathepsin a upregulation in glioma: A potential therapeutic target associated with immune infiltration

“…Glioma is the result of malignant transformation of glial cells in the white matter of the brain or spinal cord and accounts for approximately 80% of all intracranial malignancies (1). In addition, the incidence of glioma is increasing year on year with an annual growth rate of 1-2% and a 5-year survival rate of only 10-20% (2). The current treatment of glioma is mainly based on microsurgery, precise local radiotherapy, and chemotherapy, combined with preoperative three-dimensional reconstruction, intraoperative visualization navigation and postoperative gene targeting therapy (3).…”