Development and evaluation of IL13RA2 targeted drug delivery system based on glioblastoma homing peptide A2b11

Glioblastoma (GBM) is a highly aggressive brain tumor that offers few treatment options. Current therapeutic approaches face challenges such as poor drug delivery precision, low accumulation at tumor sites, and significant toxicity to normal tissues. To address these issues, this study designed a targeted drug delivery platform by modifying liposomes with the tumor-homing peptide A2b11, which specifically binds to the GBM-associated antigen IL13RA2. A2b11-liposomes loaded with sodium fluorescein (FLA) and A2b11-liposomes loaded with temozolomide (TLA) were evaluated for their anti-GBM effects. In vitro, studies demonstrated that A2b11-modified liposomes significantly enhanced accumulation in GBM cells and enhanced their anti-GBM efficacy compared to unmodified liposomes. In vivo, experiments using xenograft tumor mouse models showed that the targeted drug delivery platform exhibited good biocompatibility and in vivo safety. Compared to other organs, FLA demonstrated significantly higher accumulation at tumor sites, showcasing its potential for targeted therapy and enabling assessment of its effects on inducing apoptosis and inhibiting angiogenesis. Additionally, TLA induced GBM cell apoptosis and reduced tumor angiogenesis, highlighting its significant potential in inhibiting GBM tumor growth. The A2b11 peptide-modified liposomal system developed in this study represents a promising platform for GBM-targeted therapy. Further research and development of this platform could lay the groundwork for its future clinical application. • A2b11 peptide demonstrates stable binding with the IL13RA2 protein. • First study to modify A2b11 onto liposomes for IL13RA2-targeted GBM therapy. • A2b11 modification improves fluorescence imaging of FLA in GBM. • Enhances TLA's anti-tumor efficacy, crosses blood-brain barrier, with good safety. • A2b11-nanocarrier system shows potential for precise GBM treatment.