Theranostic Nanomedicine for Synergistic Chemodynamic Therapy and Chemotherapy of Orthotopic Glioma.
Theranostic Nanomedicine for Synergistic Chemodynamic Therapy and Chemotherapy of Orthotopic Glioma.
复制标题
用于协同化学动力疗法和原位胶质瘤化疗的治疗诊断纳米医学
DOI：
10.1002/advs.202003036
复制
发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Tan J;Duan X;Zhang F;Ban X;Mao J;Cao M;Han S;Shuai X;Shen J
胶质瘤是一种常见的原发性脑恶性肿瘤，预后较差。化疗是脑肿瘤的一线治疗方法，但药物穿过血脑屏障（BBB）的效率低，且与肿瘤缺氧相关的耐药性阻碍了其疗效。在此，通过将油酸修饰的氧化锰（MnO）和替莫唑胺（TMZ）掺入含有内化精氨酸-甘氨酸-天冬氨酸（iRGD）的聚乙二醇-聚（2-（二异丙氨基）乙基甲基丙烯酸酯）聚合物胶束中，开发了一种治疗诊断纳米药物（iRPPA@TMZ/MnO）。iRGD的存在使纳米药物具有高穿越能力。 BBB并穿透肿瘤组织后，纳米药物响应肿瘤微环境同时释放TMZ、Mn2+和O2。释放的TMZ诱导肿瘤细胞凋亡，释放的Mn2+引起细胞内氧化应激，通过类芬顿反应杀死肿瘤细胞，原位产生的O2可缓解肿瘤缺氧并增强对胶质瘤的化疗/化学动力学治疗效果。该研究表明，这种多功能纳米药物在脑胶质瘤的 MRI 可视化治疗中具有巨大潜力，该纳米药物具有穿过血脑屏障并在胶质瘤中积累的能力，可以对肿瘤微环境做出反应，从而缓解肿瘤缺氧，发挥协同化疗/化学动力学治疗的作用。磁共振成像可有效治疗原位脑胶质瘤。
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, Mn2+, and O2. The released TMZ induces tumor cell apoptosis and the released Mn2+ causes intracellular oxidative stress that kill tumor cells via a Fenton‐like reaction. The O2 produced in situ alleviates tumor hypoxia and enhances the chemotherapy/chemodynamic therapeutic effects against glioma. The Mn2+ 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. A theranostic nanodrug (iRPPA@TMZ/MnO) exhibiting a high capability of crossing the blood–brain barrier and accumulating in glioma is developed. This nanodrug can respond to the tumor microenvironment to alleviate tumor hypoxia, exert synergistic chemotherapy/chemodynamic therapy, and enable site‐specific magnetic resonance imaging for effective treatment of orthotopic brain glioma.
登录
查看更多内容
影响因子：
8
作者：
Chu Y;Chen N;Yu H;Mu H;He B;Hua H;Wang A;Sun K
通讯作者：
Sun K
影响因子：
4
作者：
Lee CY
通讯作者：
Lee CY
影响因子：
29.4
作者：
Chen, Qian;Feng, Liangzhu;Liu, Zhuang
通讯作者：
Liu, Zhuang
影响因子：
4.5
作者：
Chang, Liu;Sen Yao;Jiang, Yanyan
通讯作者：
Jiang, Yanyan
作为氧载体的基于血红蛋白的纳米结构组件
影响因子：
29.4
作者：
Jia, Yi;Duan, Li;Li, Junbai
通讯作者：
Li, Junbai