Combination of Small Molecule Prodrug and Nanodrug Delivery: Amphiphilic Drug-Drug Conjugate for Cancer Therapy
Combination of Small Molecule Prodrug and Nanodrug Delivery: Amphiphilic Drug-Drug Conjugate for Cancer Therapy
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小分子前药和纳米药物递送的组合：用于癌症治疗的两亲性药物-药物缀合物
DOI：
10.1021/ja505212y
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发表时间：
2014-08-20
影响因子：
15
通讯作者：
Yan, Deyue
中科院分区：
文献类型：
--
作者：
Huang, Ping;Wang, Dali;Yan, Deyue
所有的癌症治疗药物在到达作用点的曲折旅程中都面临着几个运输障碍。为了克服这些障碍，一种有效的癌症治疗药物输送系统势在必行。在这里，我们开发了一种用于癌症治疗的药物自递送系统，其中抗癌药物可以在没有任何载体的情况下自行递送。为了证明这种独特的方法，已经从亲水性抗癌药物伊立替康（Ir）和疏水性抗癌药物苯丁酸氮芥（Cb）通过可水解的酯键合成了两亲性药物药物缀合物（ADDC）。两亲性Ir Cb缀合物在水中自组装成纳米颗粒，并且与游离药物相比表现出更长的血液滞留半衰期，这有助于药物在肿瘤组织中的积累并促进其细胞摄取。Ir Cb ADDC纳米颗粒的纳米级特征的益处是可以有效地克服肿瘤细胞的多药耐药性（MDR）。在细胞内化后，亲水性和疏水性药物之间的酯键经历水解以释放游离的Ir和Cb，导致在体外和体内具有优异的抗癌活性。
All drugs for cancer therapy face several transportation barriers on their tortuous journey to the action sites. To overcome these barriers, an effective drug delivery system for cancer therapy is imperative. Here, we develop a drug self-delivery system for cancer therapy, in which anticancer drugs can be delivered by themselves without any carriers. To demonstrate this unique approach, an amphiphilic drug drug conjugate (ADDC) has been synthesized from the hydrophilic anticancer drug irinotecan (Ir) and the hydrophobic anticancer drug chlorambucil (Cb) via a hydrolyzable ester linkage. The amphiphilic Ir Cb conjugate self-assembles into nanopartides in water and exhibits longer blood retention half-life compared with the free drugs, which facilitates the accumulation of drugs in tumor tissues and promotes their cellular uptake. A benefit of the nanoscale characteristics of the Ir Cb ADDC nanopartides is that the multidrug resistance (MDR) of tumor cells can be overcome efficiently. After cellular internalization, the ester bond between hydrophilic and hydrophobic drugs undergoes hydrolysis to release free Ir and Cb, resulting in an excellent anticancer activity in vitro and in vivo.