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Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy
Journal of the American Chemical Society ( IF 15.0 ) Pub Date : 2020-10-22 , DOI: 10.1021/jacs.0c05381
Farah Benyettou 1 , Gobinda Das 1 , Anjana Ramdas Nair 1 , Thirumurugan Prakasam 1 , Digambar B. Shinde 2 , Sudhir Kumar Sharma 1 , Jamie Whelan 1 , Yoann Lalatonne 3, 4 , Hassan Traboulsi 5 , Renu Pasricha 1 , Osama Abdullah 1 , Ramesh Jagannathan 1 , Zhiping Lai 2 , Laurence Motte 6 , Felipe Gándara 7 , Kirsten C. Sadler 1 , Ali Trabolsi 1
Affiliation  

Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.

中文翻译:

嵌入磁性纳米颗粒的共价有机框架用于 MRI 和化学热疗

纳米级亚胺连接的共价有机框架 (nCOFs) 首先加载抗癌药物阿霉素 (Dox),涂上磁性氧化铁纳米粒子 (γ-Fe2O3 NPs),并用聚 (l-赖氨酸) 阳离子聚合物壳稳定。 PLL) 用于同步协同热化学疗法治疗和 MRI 成像。所得纳米试剂 (γ-SD/PLL) 的 pH 响应性允许药物在晚期内体和癌细胞溶酶体的酸性微环境 (pH 5.4) 内选择性释放,而不是在生理条件下 (pH 7.4)。由于 nCOF 多孔结构有利于热传导,γ-SD/PLL 在暴露于交变磁场时可以有效地产生高热量(48°C),使 γ-SD/PLL 成为水溶液中优异的热介质。由于 Dox 的协同毒性和热疗在体外对胶质母细胞瘤 U251-MG 细胞和体内对斑马鱼胚胎的影响,载药磁性 nCOF 复合材料具有细胞毒性,但它们对非癌细胞 (HEK293) 没有显着毒性。据我们所知,这是多模态 MRI 探针和化学-热疗磁性 nCOF 复合材料的第一份报告。
更新日期:2020-10-22
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