Use of size and a copolymer design feature to improve the biodistribution and the enhanced permeability and retention effect of doxorubicin-loaded mesoporous silica nanoparticles in a murine xenograft tumor model.
Use of size and a copolymer design feature to improve the biodistribution and the enhanced permeability and retention effect of doxorubicin-loaded mesoporous silica nanoparticles in a murine xenograft tumor model.
复制标题
DOI：
10.1021/nn200809t
复制
发表时间：
2011-05-24
期刊：
影响因子：
17.1
通讯作者：
Nel AE
中科院分区：
文献类型：
--
作者：
Meng H;Xue M;Xia T;Ji Z;Tarn DY;Zink JI;Nel AE
通过纳米载体改善被动药物递送至肿瘤部位的功效的关键挑战是限制网状内皮系统（RES）摄取并使增强的渗透性和保留（EPR）效应最大化。我们证明，尺寸减小和表面功能化的介孔二氧化硅纳米粒子（MSNP）与聚乙烯亚胺-聚乙二醇（PEI-PEG）共聚物减少颗粒调理作用，同时增强被动递送的单分散，50纳米阿霉素负载MSNP的人鳞状细胞癌裸鼠移植瘤静脉注射后。使用近红外（NIR）荧光成像和元素Si分析，我们证明了在肿瘤部位被动积累了约12%的注射颗粒负荷，在那里有有效的细胞摄取和多柔比星传递到KB-31细胞。与游离阿霉素相比，这伴随着细胞凋亡的诱导和肿瘤缩小率的提高。改善的药物递送伴随着全身副作用的显著减少，例如动物体重减轻以及肝和肾损伤的减少。这些结果表明，通过MSNP尺寸减小以及通过用共聚物涂覆引入空间位阻和静电排斥，可以实现有效的被动肿瘤靶向。进一步赋予这种具有靶向配体和纳米阀的多功能药物递送平台可以进一步增强细胞特异性靶向和按需释放。
A key challenge for improving the efficacy of passive drug delivery to tumor sites by a nanocarrier is to limit reticuloendothelial system (RES) uptake and to maximize the enhanced permeability and retention (EPR) effect. We demonstrate that size reduction and surface functionalization of mesoporous silica nanoparticles (MSNP) with a polyethyleneimine-polyethylene glycol (PEI-PEG) co-polymer reduces particle opsonization while enhancing the passive delivery of monodispersed, 50 nm doxorubicin-laden MSNP to a human squamous carcinoma xenograft in nude mice after intravenous injection. Using near infrared (NIR) fluorescence imaging and elemental Si analysis, we demonstrate passive accumulation of ∼12% of the injected particle load at the tumor site, where there is effective cellular uptake and the delivery of doxorubicin to KB-31 cells. This was accompanied by the induction of apoptosis and an enhanced rate of tumor shrinking compared to free doxorubicin. The improved drug delivery was accompanied by a significant reduction in systemic side effects such as animal weight loss as well as reduced liver and renal injury. These results demonstrate that it is possible to achieve effective passive tumor targeting by MSNP size reduction as well as introducing steric hindrance and electrostatic repulsion through coating with a co-polymer. Further endowment of this multifunctional drug delivery platform with targeting ligands and nanovalves may further enhance cell-specific targeting and on-demand release.
登录
查看更多内容
影响因子：
6.4
作者：
Kircheis, R;Ostermann, E;Wagner, E
通讯作者：
Wagner, E
DOI：
10.1088/0143-0815/12/4/005
发表时间：
1991-11-01
期刊：
CLINICAL PHYSICS AND PHYSIOLOGICAL MEASUREMENT
影响因子：
--
作者：
FARIS, F;THORNILEY, M;SPENCER, A
通讯作者：
SPENCER, A
影响因子：
19
作者：
Lee, Chia-Hung;Cheng, Shih-Hsun;Lo, Leu-Wei
通讯作者：
Lo, Leu-Wei
影响因子：
4.9
作者：
Li, Shyh-Dar;Huang, Leaf
通讯作者：
Huang, Leaf
介孔二氧化硅纳米粒子的体内生物分布和尿液排泄：粒径和聚乙二醇化的影响
影响因子：
13.3
作者：
He, Qianjun;Zhang, Zhiwen;Shi, Jianlin
通讯作者：
Shi, Jianlin