Lipopolymersome-mediated temozolomide delivery for IL13RA2 receptor-positive glioblastoma

Glioblastoma is the most aggressive form of primary malignant brain cancer. The blood–brain barrier limits the penetration of therapeutic agents and often contributes to a poor prognosis. Targeted therapy, an emerging strategy, shows promise for improving glioblastoma treatment outcomes by reducing drug dosages and mitigating drug resistance. Interleukin-13 receptor α2, which is overexpressed in glioblastoma, serves as a potential target for such therapy.

In this study, we investigated Pep-1L-modified, temozolomide-loaded lipopolymersomes for targeted delivery to interleukin-13 receptor α2-positive glioblastoma. These nanoparticles exhibited a uniform size of approximately 100 nm and remained stable for up to 96 h under physiological conditions (pH 7.4). Temozolomide was released in a controlled manner, reaching nearly 100 % release over 96 h. The Pep-1L peptide demonstrated specificity for interleukin-13 receptor α2-positive glioblastoma and enhanced cellular internalization via receptor-mediated endocytosis. Additionally, the IC₅₀ was reduced by approximately 9.5-fold in interleukin-13 receptor α2-positive U-251 MG cells, highlighting the potential of Pep-1L-modified, temozolomide-loaded lipopolymersomes as an effective targeted therapy for glioblastoma. This approach suggests a pathway toward more personalized and effective treatments for glioblastoma patients.