Pluronic F127-Complexed PEGylated Poly(glutamic acid)-Cisplatin Nanomedicine for Enhanced Glioblastoma Therapy

Abstract

Glioblastoma is one of the most aggressive and treatment-resistant forms of primary brain cancer, posing significant challenges in effective therapy. This study aimed to enhance the effectiveness of glioblastoma therapy by developing a unique nanomedicine composed of Pluronic F127-complexed PEGylated poly(glutamic acid)-cisplatin (PLG-PEG/PF127-CDDP). PLG-PEG/PF127-CDDP demonstrated an optimal size of 133.97 ± 12.60 nm, facilitating efficient cell uptake by GL261 glioma cells. In vitro studies showed significant cytotoxicity against glioma cells with a half-maximal (50%) inhibitory concentration (IC50) of 12.61 µg mL⁻¹ at 48 h and a 72.53% ± 1.89% reduction in cell invasion. Furthermore, PLG-PEG/PF127-CDDP prolonged the circulation half-life of cisplatin to 9.75 h in vivo, leading to a more than 50% reduction in tumor size on day 16 post-treatment initiation in a murine model of glioma. The treatment significantly elevated lactate levels in GL261 cells, indicating enhanced metabolic disruption. Therefore, PLG-PEG/PF127-CDDP offers a promising approach for glioblastoma therapy due to its effects on improving drug delivery efficiency, therapeutic outcomes, and safety while minimizing systemic side effects. This work underscores the potential of polymer-based nanomedicines in overcoming the challenges of treating brain tumors, paving the way for future clinical applications.