A Nano-in-Nano Polymer-Dendrimer Nanoparticle-Based Nanosystem for Controlled Multidrug Delivery.
A Nano-in-Nano Polymer-Dendrimer Nanoparticle-Based Nanosystem for Controlled Multidrug Delivery.
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DOI：
10.1021/acs.molpharmaceut.7b00219
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发表时间：
2017-07
影响因子：
4.9
通讯作者：
Zongmin Zhao;Song Lou;Yun Hu;Jie Zhu;Chenming Zhang
中科院分区：
文献类型：
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作者：
Zongmin Zhao;Song Lou;Yun Hu;Jie Zhu;Chenming Zhang
具有不同作用机制的多种化疗药物的联合给药是一种很有前途的癌症治疗策略。在这项研究中，我们开发了一种新的聚合物-树枝状大分子混合纳米粒子为基础的纳米系统，有效和控制的两个模型化疗药物，阿霉素（DOX）和紫杉醇（PTX）的共输送。该纳米系统的特征在于具有尺寸约为150 nm的纳米中纳米结构。通过控制投料比，可将模型药物以高载药量按比例负载到纳米体系中。此外，模型药物可以从纳米系统中释放后，一个顺序的释放方式-特异性，快速PTX释放和持续的DOX释放。发现酸性pH增强两种药物的释放。此外，纳米系统被癌细胞快速有效地吸收，并且递送的药物可以在细胞中持续有效地释放以达到其作用靶标。体外细胞毒性实验结果表明，通过优化药物配比，双载药纳米系统比单载药纳米系统或游离双载药纳米系统具有更好的抗肿瘤效果。此外，双载药纳米系统可以协同诱导细胞核和微管蛋白模式的显着变化。所有数据表明，纳米中纳米聚合物-树枝状聚合物混合纳米颗粒为基础的纳米系统是一个有前途的候选人，以实现控制的多药物输送有效的组合癌症治疗。
Codelivery of multiple chemotherapeutics with different action mechanisms is a promising strategy for cancer treatment. In this study, we developed a novel polymer-dendrimer hybrid nanoparticle-based nanosystem for efficient and controlled codelivery of two model chemotherapeutics, doxorubicin (DOX) and paclitaxel (PTX). The nanosystem was characterized to have a nano-in-nano structure with a size of around 150 nm. The model drugs could feasibly be loaded into the nanosystem ratiometrically with high drug-loading contents by controlling the feeding drug ratios. Also, the model drugs could be released from the nanosystem following a sequential release manner-specifically, quick PTX release and sustained DOX release. Acidic pH was found to enhance the release of both drugs. Moreover, the nanosystem was taken up by cancer cells rapidly and efficiently, and the delivered drugs could release sustainably and efficiently in cells to reach their action targets. In vitro cytotoxicity results demonstrated that, by optimizing drug ratios, the dual-drug-loaded nanosystem could result in better antitumor efficacy than the single-drug-loaded nanosystem or free dual-drug combination. Furthermore, the dual-drug-loaded nanosystem could induce significant changes in both the nucleus and tubulin patterns synergistically. All data suggest that the nano-in-nano polymer-dendrimer hybrid nanoparticle-based nanosystem is a promising candidate to achieve controlled multidrug delivery for effective combination cancer therapy.