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Combinatorial Intracellular Delivery Screening of Anticancer Drugs
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2020-11-11 , DOI: 10.1021/acs.molpharmaceut.0c00791
Belen Sola-Barrado 1, 2 , Diana M Leite 1, 2 , Edoardo Scarpa 1, 2 , Aroa Duro-Castano 1, 2 , Giuseppe Battaglia 1, 2, 3, 4
Affiliation  

Conventional drug solubilization strategies limit the understanding of the full potential of poorly water-soluble drugs during drug screening. Here, we propose a screening approach in which poorly water-soluble drugs are entrapped in poly(2-(methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylaminoethyl methacryate) (PMPC–PDPA) polymersomes (POs) to enhance drug solubility and facilitate intracellular delivery. By using a human pediatric glioma cell model, we demonstrated that PMPC–PDPA POs mediated intracellular delivery of cytotoxic and epigenetic drugs by receptor-mediated endocytosis. Additionally, when delivered in combination, drug-loaded PMPC–PDPA POs triggered both an enhanced drug efficacy and synergy compared to that of a conventional combinatorial screening. Hence, our comprehensive synergy analysis illustrates that our screening methodology, in which PMPC–PDPA POs are used for intracellular codelivery of drugs, allows us to identify potent synergistic profiles of anticancer drugs.

中文翻译:

抗癌药物的组合胞内递送筛选

传统的药物增溶策略限制了在药物筛选过程中对难溶于水的药物的全部潜力的理解。在这里,我们提出了一种筛选方法,其中水溶性差的药物被包裹在聚(2-(甲基丙烯酰氧基乙基磷酸胆碱)-聚(2-(二异丙基氨基乙基甲基丙烯酸))(PMPC-PDPA)聚合物囊泡中,以提高药物溶解度并促进细胞内通过使用人类小儿神经胶质瘤细胞模型,我们证明 PMPC-PDPA POs 通过受体介导的内吞作用介导细胞内细胞毒性和表观遗传药物的递送。此外,当联合递送时,载药 PMPC-PDPA POs 触发了增强的与传统组合筛选相比,药物功效和协同作用。因此,
更新日期:2020-12-07
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