Self-Assembled Nanoparticles of Amphiphilic Twin Drug from Floxuridine and Bendamustine for Cancer Therapy
Self-Assembled Nanoparticles of Amphiphilic Twin Drug from Floxuridine and Bendamustine for Cancer Therapy
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用于癌症治疗的氟尿苷和苯达莫司汀两亲性双胞胎药物的自组装纳米颗粒
DOI：
10.1021/acs.molpharmaceut.5b00005
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发表时间：
2015-07-01
影响因子：
4.9
通讯作者：
Yan, Deyue
中科院分区：
文献类型：
--
作者：
Zhang, Ting;Huang, Ping;Yan, Deyue
本文报道了一种两亲性双药策略，直接利用亲水性和疏水性小分子抗癌药物自组装成药物含量高且固定的纳米粒，解决了抗癌药物水溶性差、治疗指数低、副作用严重等问题。双药是由亲水性抗癌药物苯达莫司汀（BdM）与亲水性抗癌药物阿糖胞苷（FdU）酯化而成。由于其固有的两亲性，FdU-BdM孪生药物可以自组装成稳定和明确的纳米颗粒。FdU-BdM孪生药物进入细胞后，亲水性和疏水性药物之间的酯键很容易通过水解裂解，释放出游离的FdU和BdM。由于FdU和BdM均具有杀伤肿瘤细胞的作用，因此FdU/BdM双药纳米粒可以克服肿瘤细胞的多药耐药性，表现出良好的抗癌活性。这种策略可以扩展到其他亲水性和疏水性抗癌药物，以合成可形成纳米颗粒的亲水性孪生药物，从而自递送药物用于癌症治疗。
We report here an amphiphilic twin drug strategy directly using small molecular hydrophilic and hydrophobic anticancer drugs to self-assemble into nanoparticles with a high and fixed drug content, which can solve problems of anticancer drug delivery including poor water solubility, low therapeutic indices, and severe side effects. The twin drug has been prepared by the esterification of the hydrophilic anticancer drug floxuridine (FdU) with the hydrophobic anticancer drug bendamustine (BdM). Due to its inherent amphiphilicity, the FdU-BdM twin drug can self-assemble into stable and well-defined nanopartides. After FdU-BdM twin drug enters into cells, the ester linkage between hydrophilic and hydrophobic drugs is readily cleaved by hydrolysis to release free FdU and BdM. Since both FdU and BdM can kill cancer cells, the FdU BdM twin drug nanoparticles can overcome the multidrug resistance (MDR) of tumor cells and present an excellent anticancer activity. This strategy can be extended to other hydrophilic and hydrophobic anticancer drugs to synthesize ampliphilic twin drugs which can form nanoparticles to self-deliver drugs for cancer therapy.