LRP1-mediated pH-sensitive polymersomes facilitate combination therapy of glioblastoma in vitro and in vivo

Background: Glioblastoma (GBM) is the most invasive primary intracranial tumor, and its effective treatment is one of the most daunting challenges in oncology. The blood-brain barrier (BBB) is the main obstacle that prevents the delivery of potentially active therapeutic compounds. In this study, a new type of pH-sensitive polymersomes has been designed for glioblastoma therapy to achieve a combination of radiotherapy and chemotherapy for U87-MG human glioblastoma xenografts in nude mice and significantly increased survival time. Results: The Au-DOX@PO-ANG has a good ability to cross the blood-brain barrier and target tumors. This delivery system has pH-sensitivity and the ability to respond to the tumor microenvironment. Gold nanoparticles and doxorubicin are designed as a complex drug. This type of complex drug improve the radiotherapy (RT) effect of glioblastoma. The mice treated with Au-DOX@PO-ANG NPs have a significant reduction in tumor volume. Conclusion: In summary, a new pH-sensitive drug delivery system was fabricated for the treatment of glioblastoma. The new BBB-traversing drug delivery system potentially represents a novel approach to improve the effects of the treatment of intracranial tumors and provides hope for glioblastoma treatment.