Development of innovative nanomedicine formulations to traverse the blood-brain barrier (BBB) for effective theranostics of glioma remains a great challenge. Herein, we report the creation of macrophage membrane-camouflaged multifunctional polymer nanogels coloaded with manganese dioxide (MnO2) and cisplatin for magnetic resonance (MR) imaging-guided chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Redox-responsive poly(N-vinylcaprolactam) (PVCL) nanogels (NGs) formed via precipitation polymerization were in situ loaded with MnO2 and physically encapsulated with cisplatin to have a mean size of 106.3 nm and coated with macrophage membranes to have a good colloidal stability. The generated hybrid NGs display dual pH- and redox-responsive cisplatin and Mn(II) release profiles and can deplete glutathione (GSH) rich in tumor microenvironment through reaction with disulfide-containing cross-linkers within the NGs and MnO2. The thus created Mn(II) enables enhanced CDT through a Fenton-like reaction and T1-weighted MR imaging, while the loaded cisplatin not only exerts its chemotherapy effect but also promotes the reactive oxygen species generation to enhance the CDT efficacy. Importantly, the macrophage membrane coating rendered the hybrid NGs with prolonged blood circulation time and ability to traverse BBB for specific targeted chemotherapy/CDT of orthotopic glioma. Our study demonstrates a promising self-adaptive and cooperative NG-based nanomedicine platform for highly efficient theranostics of glioma, which may be extended to tackle other difficult cancer types.
Keywords: PVCL nanogels; blood−brain barrier; chemotherapy; enhanced chemodynamic therapy; macrophage membrane; manganese dioxide.