Intelligent design of polymer nanogels for full-process sensitized radiotherapy and dual-mode computed tomography/magnetic resonance imaging of tumors.

Development of intelligent radiosensitization nanoplatforms for imaging-guided tumor radiotherapy (RT) remains challenging. We report here the construction of an intelligent nanoplatform based on poly(-vinylcaprolactam) (PVCL) nanogels (NGs) co-loaded with gold (Au) and manganese dioxide (MnO) nanoparticles (NPs) for dual-mode computed tomography (CT)/magnetic resonance (MR) imaging-guided "full-process" sensitized RT of tumors. PVCL NGs were synthesized precipitation polymerization and loaded with Au and MnO NPs. The created PVCL-Au-MnO NGs were well characterized and systematically examined in their cytotoxicity, cellular uptake, intracellular oxygen and ·OH production, and cell cycle arrest , evaluated to disclose their RT sensitization effects of cancer cells and a tumor model, and assessed to validate their dual-mode CT/MR imaging potential, pharmacokinetics, biodistribution, and biosafety . The formed PVCL-Au-MnO NGs with a size of 121.5 nm and good stability can efficiently generate reactive oxygen species through a Fenton-like reaction to result in cell cycle distribution toward highly radiosensitive G2/M phase prior to X-ray irradiation, sensitize the RT of cancer cells under X-ray through the loaded Au NPs to induce the significant DNA damage, and further prevent DNA-repairing process after RT through the continuous production of O catalyzed by MnO in the hybrid NGs to relieve the tumor hypoxia. Likewise, the tumor RT can also be guided through dual mode CT/MR imaging due to the Au NPs and Mn(II) transformed from MnO NPs. Our study suggests an intelligent PVCL-based theranostic NG platform that can achieve "full-process" sensitized tumor RT under the guidance of dual-mode CT/MR imaging.