Biomimetic Nanosonosensitizers Combined with Noninvasive Ultrasound Actuation to Reverse Drug Resistance and Sonodynamic-Enhanced Chemotherapy against Orthotopic Glioblastoma.

Glioblastoma (GBM) is the most devastating brain tumor and highly resistant to conventional chemotherapy. Herein, we introduce biomimetic nanosonosensitizer systems (MDNPs) combined with noninvasive ultrasound (US) actuation for orthotopic GBM-targeted delivery and sonodynamic-enhanced chemotherapy. MDNPs were fabricated with biodegradable and pH-sensitive polyglutamic acid (PGA) and the chemotherapeutic agent and sonosensitizer doxorubicin (DOX), camouflaged with human GBM U87 cell membranes. MDNPs presented homologous targeting accumulation and in vivo long-term circulation ability. They effectively passed through the blood-brain barrier (BBB) under US assistance and reached the orthotopic GBM site. MDNPs exhibited controllable US-elicited sonodynamic effect by generation of reactive oxygen species (ROS). ROS not only induced cancer cell apoptosis but also downregulated drug-resistance-related factors to disrupt chemoresistance and increase sensitivity to chemotherapy. The in vivo study of orthotopic GBM treatments further proved that MDNPs exhibited US-augmented synergistic antitumor efficacy and strongly prolonged the survival rate of mice. The use of low-dose DOX and the safety of US enabled repeated treatment (4 times) without obvious cardiotoxicity. This effective and safe US-enhanced chemotherapy strategy with the advantages of noninvasive brain delivery and high drug sensitivity holds great promise for deep-seated and drug-resistant tumors.

Scaffolds biomimicking macrophages for a glioblastoma NIR-Ib imaging guided photothermal therapeutic strategy by crossing Blood-Brain Barrier.

Glioblastoma (GBM) is one of the most malignant cancers, and Blood-Brain Barrier (BBB) is the main obstacle to diagnose and treat GBM, hence scientists are making great efforts to develop new drugs which can pass BBB and integrate diagnosis and therapeutics together. Here, we designed plasma membrane of macrophage camouflaged DSPE-PEG loaded near-infrared Ib (NIR-Ib) fluorescence dye IR-792 nanoparticles (MDINPs). MDINPs were able to penetrate BBB and selectively accumulate at tumor site, and then could be used as NIR-Ib fluorescence probes for targeted tumor imaging. At the same time, MDINPs could kill tumor cells by photothermal effect. Our results showed that MDINPs-mediated NIR-Ib fluorescence imaging could clearly observe orthotopic GBM, and the NIR-Ib imaging-guided photothermal therapy significantly suppressed the growth of GBM and prolonged the life of mice. This work not only provided a method to mimic the biological function of macrophage, but also provided an integrative strategy for diagnosis and treatment in GBM.