Structure-based rational design of prodrugs to enable their combination with polymeric nanoparticle delivery platforms for enhanced antitumor efficacy.
Structure-based rational design of prodrugs to enable their combination with polymeric nanoparticle delivery platforms for enhanced antitumor efficacy.
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基于结构的前药合理设计，使其能够与聚合物纳米颗粒递送平台相结合，从而增强抗肿瘤功效。
DOI：
10.1002/anie.201406685
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发表时间：
2014-10-20
影响因子：
16.6
通讯作者：
Zheng, Shusen
中科院分区：
文献类型：
--
作者：
Wang, Hangxiang;Xie, Haiyang;Wu, Jiaping;Wei, Xuyong;Zhou, Lin;Xu, Xiao;Zheng, Shusen
载药纳米颗粒（NP）由于其在各种类型的癌症中改善的药物递送和治疗指数而对于有效的癌症治疗特别感兴趣。然而，许多化学治疗剂到递送NP中的包封通常受到其不利的物理化学性质的阻碍。在这里，我们采用药物改革策略来构建SN-38（7-乙基-10-羟基喜树碱）衍生的前药的小型文库，其中酚盐基团被各种疏水部分修饰。这种酯化作用微调了SN-38分子的极性并增强了所形成的前药的亲脂性，从而诱导它们自组装成可生物降解的聚（乙二醇）-嵌段-聚（d，l-乳酸）（PEG-PLA）纳米颗粒结构。我们的策略相结合的合理工程的前体药物与传统使用的聚合物材料的突出特点，应该开辟新的途径，设计更有效的药物输送系统作为一种治疗方式。
Drug-loaded nanoparticles (NPs) are of particular interest for efficient cancer therapy due to their improved drug delivery and therapeutic index in various types of cancer. However, the encapsulation of many chemotherapeutics into delivery NPs is often hampered by their unfavorable physicochemical properties. Here, we employed a drug reform strategy to construct a small library of SN-38 (7-ethyl-10-hydroxycamptothecin)-derived prodrugs, in which the phenolate group was modified with a variety of hydrophobic moieties. This esterification fine-tuned the polarity of the SN-38 molecule and enhanced the lipophilicity of the formed prodrugs, thereby inducing their self-assembly into biodegradable poly(ethylene glycol)-block-poly(d,l-lactic acid) (PEG-PLA) nanoparticulate structures. Our strategy combining the rational engineering of prodrugs with the pre-eminent features of conventionally used polymeric materials should open new avenues for designing more potent drug delivery systems as a therapeutic modality.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
DOI：
10.1073/pnas.1120508109
发表时间：
2012-05-22
影响因子：
11.1
作者：
Karve, Shrirang;Werner, Michael E.;Wang, Andrew Z.
通讯作者：
Wang, Andrew Z.
影响因子：
10.8
作者：
Kang, N;Perron, MÉ;Leroux, JC
通讯作者：
Leroux, JC
影响因子：
14.8
作者：
Logue, Susan E.;Elgendy, Mohamed;Martin, Seamus J.
通讯作者：
Martin, Seamus J.
影响因子：
10.8
作者：
Maeda, H;Wu, J;Hori, K
通讯作者：
Hori, K