Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA.
Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA.
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纳米结构脂质载体作为抗癌药物和siRNA肺部共递送的多功能纳米医学平台。
DOI：
10.1016/j.jconrel.2013.04.018
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发表时间：
2013-11-10
期刊：
影响因子：
--
通讯作者：
Minko T
中科院分区：
文献类型：
--
作者：
Taratula O;Kuzmov A;Shah M;Garbuzenko OB;Minko T
我们开发、合成并测试了一种基于多功能纳米结构脂质纳米载体的系统（NLCS），用于通过吸入将抗癌药物和siRNA直接有效地递送到肺部。该系统包括：（1）纳米结构脂质载体（NLC）;（2）抗癌药物（3）靶向MRP 1 mRNA的siRNA作为泵耐药性的抑制剂;（4）靶向BCL 2 mRNA的siRNA作为非泵细胞抗性的抑制剂，和（5）促黄体生成激素释放激素（LHRH）的修饰的合成类似物作为对在肺癌细胞质膜中过表达的受体具有特异性的靶向部分。使用人肺癌细胞在体外和使用人肺癌的小鼠原位模型在体内测试NLCS。吸入后，与静脉注射相比，拟议的NLCS有效地将其有效载荷递送到肺癌细胞中，使健康肺组织保持完整，并显著降低健康器官的暴露量。与静脉给药相比，NLCS显示出增强的抗肿瘤活性。所获得的数据证明了所提出的NLCS通过吸入抗癌药物和特异性针对肺癌细胞的siRNA混合物进行肿瘤靶向局部递送的高效率，并且因此有效抑制肿瘤生长并预防对健康器官的不良副作用。
We developed, synthesized, and tested a multifunctional nanostructured lipid nanocarrier-based system (NLCS) for efficient delivery of an anticancer drug and siRNA directly into the lungs by inhalation. The system contains: (1) nanostructured lipid carriers (NLC); (2) anticancer drug (doxorubicin or paclitaxel); (3) siRNA targeted to MRP1 mRNA as a suppressor of pump drug resistance; (4) siRNA targeted to BCL2 mRNA as a suppressor of nonpump cellular resistance and (5) a modified synthetic analog of luteinizing hormone-releasing hormone (LHRH) as a targeting moiety specific to the receptors that are overexpressed in the plasma membrane of lung cancer cells. The NLCS was tested in vitro using human lung cancer cells and in vivo utilizing mouse orthotopic model of human lung cancer. After inhalation, the proposed NLCS effectively delivered its payload into lung cancer cells leaving healthy lung tissues intact and also significantly decreasing the exposure of healthy organs when compared with intravenous injection. The NLCS showed enhanced antitumor activity when compared with intravenous treatment. The data obtained demonstrated high efficiency of proposed NLCS for tumor-targeted local delivery by inhalation of anticancer drugs and mixture of siRNAs specifically to lung cancer cells and, as a result, efficient suppression of tumor growth and prevention of adverse side effects on healthy organs.
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影响因子：
5.4
作者：
Betigeri, Seema;Zhang, Min;Garbuzenko, Olga;Minko, Tamara
通讯作者：
Minko, Tamara
影响因子：
10.8
作者：
Dharap, SS;Qiu, B;Minko, T
通讯作者：
Minko, T
DOI：
10.1073/pnas.0504274102
发表时间：
2005-09-06
影响因子：
11.1
作者：
Dharap, SS;Wang, Y;Minko, T
通讯作者：
Minko, T
影响因子：
4.9
作者：
Chandna, Pooja;Saad, Maha;Minko, Tamara
通讯作者：
Minko, Tamara
影响因子：
3.7
作者：
Garbuzenko, Olga B.;Saad, Maha;Minko, Tamara
通讯作者：
Minko, Tamara