Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line.
Engineered design of mesoporous silica nanoparticles to deliver doxorubicin and P-glycoprotein siRNA to overcome drug resistance in a cancer cell line.
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DOI：
10.1021/nn100690m
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发表时间：
2010-08-24
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;Liong M;Xia T;Li Z;Ji Z;Zink JI;Nel AE
P-糖蛋白(P-gp)等药物外排转运蛋白的过度表达是肿瘤细胞产生多药耐药(MDR)的主要机制之一。克服多药耐药的一种新方法是采用联合传递策略，利用siRNA沉默外排转运蛋白的表达，并与适当的抗癌药物一起用于耐药细胞。在本文中，我们报道了介孔二氧化硅纳米颗粒(MSNP)可以功能化，有效地将化疗药物阿霉素(Dox)和Pgp siRNA输送到耐药癌细胞系(KB-V1细胞)，以相加或协同的方式完成对细胞的杀伤。颗粒表面带有膦酸基的官能化允许Dox与多孔内部的静电结合，在非生物和生物条件下，通过酸化介质可以从那里释放药物。此外，磷酸盐修饰还允许在外部涂覆阳离子聚合物聚乙烯亚胺(PEI)，使MSNP同时提供PGP siRNA。在KB-V1细胞中，Dox和siRNA的双重传递能够增加细胞内和核内的药物浓度，达到超过游离Dox或在没有siRNA联合传递的情况下由MSNP传递的药物的水平。这些结果表明，使用MSNP平台有效地传递siRNA是可能的，该siRNA可以下调药物输出子的基因表达，从而可以用来提高对化疗药物的敏感性。
Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) protein is one of the major mechanisms for multiple drug resistance (MDR) in cancer cells. A new approach to overcome MDR is to use a co-delivery strategy that utilizes a siRNA to silence the expression of efflux transporter together with an appropriate anti-cancer drug for drug resistant cells. In this paper, we report that mesoporous silica nanoparticles (MSNP) can be functionalized to effectively deliver a chemotherapeutic agent doxorubicin (Dox) as well as Pgp siRNA to a drug-resistant cancer cell line (KB-V1 cells) to accomplish cell killing in an additive or synergistic fashion. The functionalization of the particle surface with a phosphonate group allows electrostatic binding of Dox to the porous interior, from where the drug could be released by acidification of the medium under abiotic and biotic conditions. In addition, phosphonate modification also allows exterior coating with the cationic polymer, polyethylenimine (PEI), which endows the MSNP contemporaneously deliver Pgp siRNA. The dual delivery of Dox and siRNA in KB-V1 cells was capable of increasing the intracellular as well as intranuclear drug concentration to levels exceeding that of free Dox or the drug being delivered by MSNP in the absence of siRNA co-delivery. These results demonstrate that it is possible to use the MSNP platform to effectively deliver a siRNA that knocks down gene expression of a drug exporter that can be used to improve drug sensitivity to a chemotherapeutic agent.
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影响因子：
13.3
作者：
Chen, Alex M.;Zhang, Min;Wei, Dongguang;Stueber, Dirk;Taratula, Oleh;Minko, Tamara;He, Huixin
通讯作者：
He, Huixin
影响因子：
17.1
作者：
Xia, Tian;Kovochich, Michael;Liong, Monty;Meng, Huan;Kabehie, Sanaz;George, Saji;Zink, Jeffrey I.;Nel, Andre E.
通讯作者：
Nel, Andre E.
影响因子：
3.9
作者：
Bagwe, RP;Hilliard, LR;Tan, WH
通讯作者：
Tan, WH
影响因子：
4.9
作者：
Santra, S;Yang, H;Mericle, RA
通讯作者：
Mericle, RA
影响因子：
8.6
作者：
Lin, Yu-Shen;Haynes, Christy L.
通讯作者：
Haynes, Christy L.