Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study.
Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study.
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DOI：
10.3390/pharmaceutics12121242
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发表时间：
2020-12-20
期刊：
影响因子：
5.4
通讯作者：
Etrych T
中科院分区：
文献类型：
--
作者：
Kudláčová J;Kotrchová L;Kostka L;Randárová E;Filipová M;Janoušková O;Fang J;Etrych T
纳米药物是一类新型的治疗药物，得益于药物载体的纳米尺寸。这些纳米系统主要在癌症治疗中非常有利，因为它们增强了肿瘤的积累。通常用于常规纳米治疗临床前评估的单层肿瘤细胞不具有空间结构结构，因此无法对纳米药物的渗透进行研究，从而预测其在真实肿瘤组织中的行为。因此，我们以结肠癌C26细胞和胶质母细胞瘤U87-MG细胞的肿瘤球体为三维体外模型，分析了携带抗癌药物吡柔比星（THP）的N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物纳米药物的内部结构、水动力大小、分散性和生物降解性对球体穿透性的影响。虽然观察到线状共聚物和星形共聚物以及它们与THP的偶联物的穿透力几乎相同，但纳米药物应用后THP的穿透力要比自由THP深得多，从而证明了聚合物载体的好处。THP聚合物纳米药物对肿瘤细胞球体的细胞毒性与游离THP几乎相同，而这些纳米药物的二维细胞毒性通常较低。因此，纳米药物在更真实的三维肿瘤细胞球体系统中证明了增强的功效。
Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics do not have a spatial structural architecture that allows the investigation of the penetration of nanomedicines to predict their behavior in real tumor tissue. Therefore, tumor spheroids from colon carcinoma C26 cells and glioblastoma U87-MG cells were used as 3D in vitro models to analyze the effect of the inner structure, hydrodynamic size, dispersity, and biodegradability of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based nanomedicines carrying anticancer drug pirarubicin (THP) on the penetration within spheroids. While almost identical penetration through spheroids of linear and star-like copolymers and also their conjugates with THP was observed, THP penetration after nanomedicines application was considerably deeper than for the free THP, thus proving the benefit of polymer carriers. The cytotoxicity of THP-polymer nanomedicines against tumor cell spheroids was almost identical as for the free THP, whereas the 2D cell cytotoxicity of these nanomedicines is usually lower. The nanomedicines thus proved the enhanced efficacy within the more realistic 3D tumor cell spheroid system.
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影响因子：
6.7
作者：
Klepac, Damir;Kostkova, Hana;Filippov, Sergey K.
通讯作者：
Filippov, Sergey K.
DOI：
10.1016/j.ejpb.2014.10.007
发表时间：
2015-02-01
影响因子：
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DOI：
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发表时间：
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影响因子：
11.1
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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