Theranostic Nanomedicine for Synergistic Chemodynamic Therapy and Chemotherapy of Orthotopic Glioma.

Glioma is a common primary brain malignancy with a poor prognosis. Chemotherapy is the first-line treatment for brain tumors but low efficiency of drugs in crossing the blood-brain barrier (BBB) and drug resistance related to tumor hypoxia thwart its efficacy. Herein, a theranostic nanodrug (iRPPA@TMZ/MnO) is developed by incorporating oleic acid-modified manganese oxide (MnO) and temozolomide (TMZ) into a polyethylene glycol-poly(2-(diisopropylamino)ethyl methacrylate-based polymeric micelle containing internalizing arginine-glycine-aspartic acid (iRGD). The presence of iRGD provides the nanodrug with a high capacity of crossing the BBB and penetrating the tumor tissue. After accumulation in glioma, the nanodrug responds to the tumor microenvironment to simultaneously release TMZ, Mn, and O. The released TMZ induces tumor cell apoptosis and the released Mn causes intracellular oxidative stress that kill tumor cells via a Fenton-like reaction. The O produced in situ alleviates tumor hypoxia and enhances the chemotherapy/chemodynamic therapeutic effects against glioma. The Mn can also serve as a magnetic resonance imaging (MRI) contrast agent for tumor imaging during therapy. The study demonstrates the great potential of this multifunctional nanodrug for MRI-visible therapy of brain glioma.