Multi-functional F127-grafted vitamin E succinate-modified liposomes for enhancing glioma therapy

Abstract

In glioma treatment, the poor penetration of therapeutic drugs through the blood–brain barrier (BBB) to the tumor region, along with the intrinsic resistance of glioma cells via multiple survival mechanisms, remain major challenges. Liposomes are a popular choice for glioma therapy due to their ability to help drugs penetrate the BBB. However, unmodified liposomes have drawbacks, such as poor stability, low drug entrapment efficacy, and rapid removal from circulation, leading to reduced drug absorption at the lesion sites. To address these issues, a novel F127-grafted vitamin E succinate (F127–VES) was designed to prepare multifunctional modified liposomes for delivery of harmine (HAR). Compared to conventional liposomes (Ordinary-Lip), F127–VES-Lip shows greater potential in enhancing the anti-glioma effect of HAR. This is attributed to several key features: Firstly, Pluronic can enhance the transport across the blood–brain barrier. Secondly, the presence of F127 in the formulation extends the circulation time of the drug in the bloodstream. Finally, the combination of F127 and VES in F127–VES-Lip can induce tumor cell apoptosis. In vitro and in vivo results confirmed that the F127–VES-Lip could significantly elevate cellular uptake, promote apoptosis and increase the antitumor effect for C6 glioma cells. The F127–VES-Lip is a promising nanoformulation to enhance the effect of HAR for glioma treatment.