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Delaying Anticancer Drug Delivery by Self‐Assembly and Branching Effects of Minimalist Dendron–Drug Conjugates
Chemistry - A European Journal ( IF 3.9 ) Pub Date : 2018-06-28 , DOI: 10.1002/chem.201801092 Florian Correard 1, 2 , Myriam Roy 3 , Vincent Terrasson 3 , Diane Braguer 1, 2 , Marie‐Anne Estève 1, 2 , Marc Gingras 3
Chemistry - A European Journal ( IF 3.9 ) Pub Date : 2018-06-28 , DOI: 10.1002/chem.201801092 Florian Correard 1, 2 , Myriam Roy 3 , Vincent Terrasson 3 , Diane Braguer 1, 2 , Marie‐Anne Estève 1, 2 , Marc Gingras 3
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Self‐assembly of a covalently‐bound lipophilic drug to a dendronic scaffold for making organic nanoparticles is reported as a proof of concept in nanovectorization. A minimalist structural approach with a small PEG‐dendron conjugated to paclitaxel (PTX), incorporating safe succinic and gallic acids, is efficient to provide the expected anticancer bioactivity, but also significantly retards and targets intracellular delivery of PTX in 2D and 3D lung cancer cell cultures. A branching effect of dendrons is crucial, when compared to linear PTX conjugates. Transmission electron microscopy (TEM) and dynamic light‐scattering (DLS) studies indicate the formation of stable, low‐disperse nanoparticles at 10−5 m in H20, which could also be responsible for the biological effects. An ultrasensitive LC‐MS/MS method was used for the determination of intracellular PTX concentration over time, along with the survival rates of cancer cells. Similarly, cell survival assays were successfully correlated to a 3D cell culture with spheroids for mimicking tumors, when treated with PTX conjugates. Our work opens the way to a full evaluation program required for new chemical entities.
中文翻译：
极简Dendron-Drug共轭物的自组装和分支效应延迟了抗癌药物的递送。
据报道，将共价结合的亲脂性药物自组装至树突状支架以制备有机纳米颗粒，是纳米载体化概念的证明。使用结合有安全的琥珀酸和没食子酸的小型PEG-紫杉醇（紫杉醇（PTX））结合的极简主义结构方法可有效提供预期的抗癌生物活性，而且还可以显着阻滞并靶向2D和3D肺癌细胞中PTX的细胞内递送。文化。与线性PTX共轭物相比，树突的支化作用至关重要。透射电子显微镜（TEM）和动态光散射（DLS）研究表明，H 2中10 -5 m处形成稳定的低分散纳米颗粒0，也可能是造成生物学效应的原因。一种超灵敏的LC-MS / MS方法用于确定随时间推移的细胞内PTX浓度以及癌细胞的存活率。类似地，当用PTX偶联物处理时，细胞存活率测定已成功地与带有球体的3D细胞培养物进行了模拟，以模拟肿瘤。我们的工作为新化学实体所需的全面评估计划开辟了道路。
更新日期：2018-06-28
中文翻译：
极简Dendron-Drug共轭物的自组装和分支效应延迟了抗癌药物的递送。
据报道，将共价结合的亲脂性药物自组装至树突状支架以制备有机纳米颗粒，是纳米载体化概念的证明。使用结合有安全的琥珀酸和没食子酸的小型PEG-紫杉醇（紫杉醇（PTX））结合的极简主义结构方法可有效提供预期的抗癌生物活性，而且还可以显着阻滞并靶向2D和3D肺癌细胞中PTX的细胞内递送。文化。与线性PTX共轭物相比，树突的支化作用至关重要。透射电子显微镜（TEM）和动态光散射（DLS）研究表明，H 2中10 -5 m处形成稳定的低分散纳米颗粒0，也可能是造成生物学效应的原因。一种超灵敏的LC-MS / MS方法用于确定随时间推移的细胞内PTX浓度以及癌细胞的存活率。类似地，当用PTX偶联物处理时，细胞存活率测定已成功地与带有球体的3D细胞培养物进行了模拟，以模拟肿瘤。我们的工作为新化学实体所需的全面评估计划开辟了道路。
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