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Τρίτη 10 Αυγούστου 2021

Lidocaine liposome modified with folic acid suppresses the proliferation and motility of glioma cells via targeting the PI3K/AKT pathway

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Exp Ther Med. 2021 Sep;22(3):1025. doi: 10.3892/etm.2021.10457. Epub 2021 Jul 15.

ABSTRACT

Glioma is life-threatening tumor of the central nervous system. Although lidocaine is usually used as local anesthetic, it also has antitumor effects. However, its clinical application in glioma is hampered by limited distribution to the brain. The aim of the present study was to enhance the ability of lidocaine to penetrate the blood-brain barrier (BBB) to target glioma and investigate its antitumor mechanism. A folic acid (FA)-modified lidocaine-carrying liposome (Lid-FA-Lip) was prepared, and its particle size, ζ potential, encapsulation efficiency, release profile stability and hemolytic effect were characterized in vitro. The targeting capacity and antitumor activities of Lid-FA-Lip were also investigated in vitro and in vivo. The results indicated that the modification of liposomes with FA significantly improved the ab ility of lidocaine to cross the BBB in an in vitro model and increased its uptake by U87 cells. Additionally, Lid-FA-Lip significantly suppressed the motility of U87 glioma cells and stimulated apoptosis. Furthermore, the results confirmed that Lid-FA-Lip targeted the PI3K/AKT pathway and suppressed the growth of glioma xenografts in mice. In summary, the study demonstrated that Lid-FA-Lip is a promising liposomal formulation of lidocaine that may provide improved therapeutic effects on glioma, mediated via the PI3K/AKT pathway.

PMID:34373711 | PMC:PMC8343891 | DOI:10.3892/etm.2021.10457

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