Manganese Dioxide‐Based Nanocarrier Delivers Paclitaxel to Enhance Chemotherapy against Orthotopic Glioma through Hypoxia Relief

Abstract Chemotherapy plays an important role in treating cancers in clinic. Hypoxia‐mediated chemoresistance remains a major hurdle for effective tumor chemotherapy. Herein, a new class of tLyP‐1‐modified dopamine (DOPA)‐β‐cyclodextrin (CD)‐coated paclitaxel (PTX)‐ and manganese dioxide (MnO 2 )‐loaded nanoparticles (tLyP‐1‐CD‐DOPA‐MnO 2 @PTX) is developed to enhance glioma chemotherapy. The nanomedicine delivered to the tumor site decomposes in response to the weak acidity and high hydrogen peroxide in the tumor microenvironment (TME), resulting in collapse of the system to release PTX and generates Mn 2+ and O 2 . In a rat model of intracranial glioma, tLyP‐1‐CD‐DOPA‐MnO 2 @PTX can efficiently pass through the blood‐brain‐barrier to accumulate in tumor sites. The hypoxia in TME can be relieved via O 2 generated by MnO 2 and the reactive oxygen species produced by Mn 2+ can kill tumor cells. The tLyP‐1‐CD‐DOPA‐MnO 2 @PTX nanoparticles exert a remarkable antitumor effect by promoting apoptosis and inhibiting proliferation of tumor cells in addition to enabling real‐time tumor monitoring with magnetic resonance imaging. This MnO 2 ‐based theranostic medicine will offer a novel strategy to simultaneously enhance chemotherapy and achieve real‐time imaging of therapeutic process in glioma treatment.