State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, P. R. China.
Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P. R. China.
Theranostics. 2022 Apr 18;12(7):3420-3437. doi: 10.7150/thno.70346. eCollection 2022.
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.
用于成像引导肿瘤放射治疗（RT）的智能增敏纳米平台的开发仍然具有挑战性。我们在此报告了一种基于聚（己内酯）（PVCL）纳米凝胶（NG）的智能纳米平台的构建，该纳米平台共载有金（Au）和二氧化锰（MnO）纳米颗粒（NPs），用于双模式计算机断层扫描（CT）/磁共振（MR）成像引导的“全流程”增敏肿瘤 RT。PVCL NG 通过沉淀聚合合成并负载 Au 和 MnO NPs。所创建的 PVCL-Au-MnO NG 进行了很好的特征描述和系统检查，包括细胞毒性、细胞摄取、细胞内氧和·OH 产生以及细胞周期停滞，以揭示其对癌细胞和肿瘤模型的 RT 增敏作用，并评估其双模式 CT/MR 成像潜力、药代动力学、生物分布和生物安全性。形成的 PVCL-Au-MnO NG 尺寸为 121.5nm，具有良好的稳定性，可以通过芬顿样反应有效地生成活性氧，导致细胞周期分布在 X 射线照射前向高度敏感的 G2/M 期，通过负载的 Au NPs 对癌细胞的 RT 增敏，导致明显的 DNA 损伤，并通过混合 NG 中 MnO 持续产生的 O 进一步阻止 RT 后的 DNA 修复过程，以缓解肿瘤缺氧。同样，由于 Au NPs 和从 MnO NPs 转化而来的 Mn（II），肿瘤 RT 也可以通过双模式 CT/MR 成像来指导。我们的研究表明，基于智能 PVCL 的治疗学 NG 平台可以在双模式 CT/MR 成像的指导下实现“全流程”肿瘤 RT 增敏。
