Ligand-metal-drug coordination based micelles for efficient intracellular doxorubicin delivery
Ligand-metal-drug coordination based micelles for efficient intracellular doxorubicin delivery
复制标题
基于配体-金属-药物配位的胶束，用于有效的细胞内阿霉素递送
DOI：
10.1039/c5ra05747g
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发表时间：
2015-01-01
期刊：
影响因子：
3.9
通讯作者：
Wang, Yu-zhong
中科院分区：
文献类型：
--
作者：
Bai, Lan;Song, Fei;Wang, Yu-zhong
在抗癌药物的传递领域，如何提高载体的载药量，同时实现高效的细胞内药物转运是一个非常困难的问题，也是化疗发展的重要课题。本文采用响应pH的可逆配体-金属-药物配位结构来构建智能药物递送系统，其中配体和金属可以被视为港口和锚，以不仅使药物（多柔比星，DOX）摩尔停泊，而且使货物精确地按时发送。根据该策略，系统的DOX载药量可达26.1%。由于配位键在中性条件下的稳定性，过早的药物泄漏被极大地抑制到低于5%，而由于键的断裂，在pH 5.0下实现了几乎完全的药物释放。配位相互作用的存在对DOX的控制释放起着关键作用，在非配位体系中，DOX的控制释放遵循一级动力学模型，而在配位体系中，DOX的控制释放遵循准二级动力学模型。此外，金属配位系统可以有效地将DOX带入HeLa细胞，表现出与游离DOX相当的癌症治疗效果。本研究建立了利用协同作用连接药物和载体作为一种有前途的方式，以满足迫切需要的化疗。
In the field of anticancer drug delivery, improving drug loading capacity of carriers and achieving efficient intracellular drug transportation simultaneously is very difficult but they are important issues for the development of chemotherapy. Herein, a reversible ligand-metal-drug coordination architecture responsive to pH was employed to construct a smart drug delivery system, in which the ligand and metal can be regarded as a harbor and an anchor to not only moor the drug (doxorubicin, DOX) but also send the cargo precisely on time. Based on the strategy, DOX loading content of the system could run up to 26.1%. Owing to the stability of coordination bonds at neutral conditions, premature drug leakage was extremely suppressed to lower than 5%, while an almost complete drug release was realized at pH 5.0 as a result of breakage of the bonds. Presence of the coordination interaction played a key role in controlled release of DOX, which followed the first-order kinetics model in the case of non-coordinated systems but the pseudo-second-order kinetics model in the case of coordinated systems. Moreover, the metal-coordinated system could effectively take DOX into HeLa cells, presenting a comparable cancer therapy effect to free DOX. This study established exploitation of coordination interaction to connect drugs and carriers as a promising way to meet urgent needs for chemotherapy.