Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells.
Delivering hydrophilic and hydrophobic chemotherapeutics simultaneously by magnetic mesoporous silica nanoparticles to inhibit cancer cells.
复制标题
通过磁性介孔二氧化硅纳米颗粒同时传递亲水性和疏水性化疗药物以抑制癌细胞
DOI：
10.2147/ijn.s28088
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发表时间：
2012
影响因子：
8
通讯作者：
Gu H
中科院分区：
文献类型：
--
作者：
Liu Q;Zhang J;Sun W;Xie QR;Xia W;Gu H
使用纳米颗粒输送化疗药物为癌症治疗提供了新的机会，但当它们被用于多种药物输送时，尤其是在联合疗法中同时输送亲水和疏水药物时，仍然存在挑战。在本文中，我们开发了一种利用磁性介孔二氧化硅纳米颗粒(MMSN)来传递亲水-疏水抗癌药物对的方法。我们制备了平均孔径为50 nm的MMSN，并通过从阿霉素水溶液和紫杉醇或雷帕霉素的非水溶液中顺序吸附的方法，评价了它们对阿霉素-紫杉醇和阿霉素-雷帕霉素两种化疗药物组合的负载能力。实验结果表明，该策略成功地实现了亲水药物和疏水药物的共负载，载药量高，比例可调范围宽。我们详细阐述了硅羟基和药物分子之间的分子相互作用背后的理论，这是可控负载和随后药物对释放的基础。与单药MMSN相比，多药MMSN更容易被A549人肺腺癌细胞内化，并产生更强的肿瘤细胞凋亡和生长抑制作用。因此，我们的研究实现了亲水和疏水药物的同时给药和剂量可调，使其具有更好的抗癌效果。这一策略可以很容易地推广到其他化疗组合，并可能具有临床可翻译的意义。
Using nanoparticles to deliver chemotherapeutics offers new opportunities for cancer therapy, but challenges still remain when they are used for the delivery of multiple drugs, especially for the synchronous delivery of hydrophilic and hydrophobic drugs in combination therapies. In this paper, we developed an approach to deliver hydrophilic–hydrophobic anticancer drug pairs by employing magnetic mesoporous silica nanoparticles (MMSNs). We prepared 50 nm-sized MMSNs with uniform pore size and evaluated their capability for the loading of two combinations of chemotherapeutics, namely doxorubicin–paclitaxel and doxorubicin–rapamycin, by means of sequential adsorption from the aqueous solution of doxorubicin and nonaqueous solutions of paclitaxel or rapamycin. Experimental results showed that the present strategy successfully realized the co-loading of hydrophilic and hydrophobic drugs with high-loading content and widely tunable ratio range. We elaborate on the theory behind the molecular interaction between the silica hydroxyl groups and drug molecules, which underlie the controllable loading, and the subsequent release of the drug pairs. Then we demonstrate that the multidrug-loaded MMSNs could be easily internalized by A549 human pulmonary adenocarcinoma cells, and produce enhanced tumor cell apoptosis and growth inhibition as compared to single-drug loaded MMSNs. Our study thus realized simultaneous and dose-tunable delivery of hydrophilic and hydrophobic drugs, which were endowed with improved anticancer efficacy. This strategy could be readily extended to other chemotherapeutic combinations and might have clinically translatable significance.