Drug-Specific Design of Telodendrimer Architecture for Effective Doxorubicin Encapsulation.
Drug-Specific Design of Telodendrimer Architecture for Effective Doxorubicin Encapsulation.
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DOI：
10.1021/acs.jpcb.6b06070
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
Wenjuan Jiang;Xiaoyi Wang;Dandan Guo;Juntao Luo;S. Nangia
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作者：
Wenjuan Jiang;Xiaoyi Wang;Dandan Guo;Juntao Luo;S. Nangia
设计一个多功能的纳米载体平台，可以定制提供特定的药物有效载荷是具有挑战性的。通常，有效的药物包封、高载药量、均匀的形状和尺寸分布以及增强的稳定性是成功的纳米载体设计的基本属性。纳米载体的这些物理化学特征与它们负责递送的特定药物有效载荷密切相关。纳米载体支架的分子结构通常需要针对每种药物进行调整，特别是如果靶药物在结构和化学上不同，如阿霉素（DOX）和紫杉醇（PTX）的情况。从我们先前报道的优化PTX的末端树枝状聚合物嵌段共聚物平台开始，我们分析了三代末端树枝状聚合物架构，以达到能够封装另一种重要的化疗药物DOX的设计。在原子级和粗粒度分辨率下进行多个长时间尺度的自组装模拟，以产生平衡的DOX包封的纳米载体。结果表明，在分子结构的telodendrimer头基团的微妙变化有深远的影响，纳米载体的大小，形态和非球面性。模拟结果与阿霉素包封纳米载体的实验数据一致。这项工作强调了分子模拟在纳米载体的合理设计中越来越重要的作用，从而消除了在实验合成中普遍存在的试错法。从模拟中获得的分子水平的见解将用于设计下一代药物特异性纳米载体。
Designing a versatile nanocarrier platform that can be tailored to deliver specific drug payloads is challenging. In general, effective drug encapsulation, high drug-loading capacity, uniform shape and size distribution, and enhanced stability are among the fundamental attributes of a successful nanocarrier design. These physiochemical features of the nanocarriers are intimately tied to the specific drug payload that they are tasked to deliver. The molecular architecture of the nanocarrier's scaffold often needs to be tuned for each drug, especially if the target drugs are structurally and chemically distinct as in the case of doxorubicin (DOX) and paclitaxel (PTX). Starting from our previously reported telodendrimeric block copolymer platform optimized for PTX, we analyze three generations of telodendrimer architectures to arrive at the design that is capable of encapsulating another important chemotherapeutic drug, DOX. Multiple long-time-scale self-assembly simulations were performed both in atomistic and coarse-grained resolutions to generate equilibrated DOX-encapsulated nanocarriers. The results show how subtle changes in the molecular architecture of the telodendrimer head groups have profound effects on the nanocarrier size, morphology, and asphericity. The simulation results are in agreement with the experimental data for DOX-encapsulated nanocarriers. This work emphasizes the increasing role of molecular simulations in the rational design of nanocarriers, thereby eliminating the trial and error method that has been prevalent in experimental synthesis. The molecular-level insights gained from the simulations will be used to design the next generation of drug-specific nanocarriers.