Abstract
BACKGROUND: Due to the presence of the blood-brain barrier, the efficacy of chemotherapy for glioblastoma has remained suboptimal. Even drugs capable of crossing the BBB, such as temozolomide, exhibit limited therapeutic outcomes owing to insufficient targeting. METHODS: Here, we developed a platelet membrane-hybridized biomimetic microbubble by loading superparamagnetic iron oxide and temozolomide-embedded polymers, constructing an ultrasound-controlled platelet membrane-inspired magnetic targeting drug delivery platform (ST-PM). Extensive in vitro and in vivo experimental results demonstrate that ST-PM exhibits inhibitory effects on glioblastoma under the combined action of a magnetic field and focused ultrasound. RESULTS: The results demonstrated that ST-PM significantly enhanced microbubble stability in vivo while preserving both the magnetic targeting capability of magnetic drugs and the ultrasound-sensitizing properties of microbubbles. In orthotopic tumor mouse models, ST-PM exhibited superior tumor-targeting efficiency and markedly inhibited tumor growth. Furthermore, H&E staining of major organs confirmed the biosafety of ST-PM. CONCLUSION: The platelet membrane enhances the stability of drug-loaded microbubbles, facilitating targeted drug accumulation at the lesion site. These findings propose a novel treatment strategy with clinical translation potential for glioblastoma management.