Smart platelet-based biohybrid delivery system for magnetic-guided targeted delivery and enhanced photothermal-chemo therapy against glioma

Glioma, as a fatal tumor, is difficult to treat for the poor blood-brain barrier (BBB), blood-brain tumor barrier (BBTB) penetrance and tumor targeting of drugs. There is an urgent need to develop effective strategies to solve the problem of tumor penetration and targeting. Herein, we fabricated a platelet-based biohybrid delivery system (FeDN@P), integrating dual photothermal, reactive oxygen species (ROS) responsive therapeutic nanoparticles (DPT NPs) and magnetic nanoparticles into platelets. Driven by the magnetic field, FeDN@P autonomously aggregate in the brain and subsequently cross BBB/BBTB through tumor aggregative properties of platelets. Triggered by the external laser, the loaded therapeutic DPT NPs are on-site secreted to penetrate deep tumor, and subsequently, spatio-temporal controlled release of doxorubicin (Dox) by the hyperthermia and tumor ROS. Establishing the subcutaneous and orthotopic C6 glioma bearing nude mice, the results illustrate that the FeDN@P has superior magnetic-guided active tumor targeting and retention. Moreover, effective inhibition of tumor proliferation and significantly prolonged medium survival time are achieved with the photothermal-chemo combined therapy. These data demonstrated that this biohybrid platelet delivery system advanced the active target delivery, on-demand drug release, and noninvasive precise photothermal-chemo therapy for glioma, which provided a promising strategy for precision tumor therapy in the future.