A drug-specific nanocarrier design for efficient anticancer therapy.
A drug-specific nanocarrier design for efficient anticancer therapy.
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DOI：
10.1038/ncomms8449
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发表时间：
2015-07-09
影响因子：
16.6
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Shi C;Guo D;Xiao K;Wang X;Wang L;Luo J
纳米载体的载药性能取决于其结构单元的化学结构和性质。在这里，我们定制末端树枝状聚合物（线性树枝状共聚物）来设计具有改进的体内药物递送特征的纳米载体。我们做了一个小分子库的虚拟屏幕，以确定使用肽化学精确telodendrimer合成的最佳构建模块。与合理设计的telodendrimer架构，然后，我们通过引入一个最佳的药物结合分子（DBM），而不牺牲纳米载体的稳定性，优化纳米载体的药物结合亲和力。为了验证计算的预测，我们合成了一系列的纳米载体和系统地评估阿霉素交付。含大黄酸的纳米载体具有持续的药物释放、延长的循环、增加的耐受剂量、降低的毒性、有效的肿瘤靶向和上级的抗癌作用，这归因于有利的阿霉素结合亲和力和改善的纳米颗粒稳定性。这项研究表明，从头设计的telodendrimer纳米载体的特定药物分子的可行性和通用性，这是一个很有前途的方法来改变纳米载体的药物输送的发展。
The drug-loading properties of nanocarriers depend on the chemical structures and properties of their building blocks. Here, we customize telodendrimers (linear-dendritic copolymer) to design a nanocarrier with improved in vivo drug delivery characteristics. We do a virtual screen of a library of small molecules to identify the optimal building blocks for precise telodendrimer synthesis using peptide chemistry. With rationally designed telodendrimer architectures, we then optimize the drug binding affinity of a nanocarrier by introducing an optimal drug-binding molecule (DBM) without sacrificing the stability of the nanocarrier. To validate the computational predictions, we synthesize a series of nanocarriers and evaluate systematically for doxorubicin delivery. Rhein-containing nanocarriers have sustained drug release, prolonged circulation, increased tolerated dose, reduced toxicity, effective tumor targeting and superior anticancer effects owing to favourable doxorubicin-binding affinity and improved nanoparticle stability. This study demonstrates the feasibility and versatility of the de novo design of telodendrimer nanocarriers for specific drug molecules, which is a promising approach to transform nanocarrier development for drug delivery.