Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment.
Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment.
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DOI：
10.1016/j.nano.2017.11.010
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Ramesh R
中科院分区：
文献类型：
--
作者：
Amreddy N;Babu A;Panneerselvam J;Srivastava A;Muralidharan R;Chen A;Zhao YD;Munshi A;Ramesh R
联合使用功能不同的抗癌药物已成为肺癌治疗的有效策略。然而，需要专门设计的药物递送系统来共同封装功能不同的药物，例如 siRNA 和化疗的组合，以进行靶向递送。我们开发了一种基于叶酸（FA）缀合的聚酰胺胺树状聚合物（Den）的纳米颗粒（NP）系统，用于将针对HuR mRNA（HuR siRNA）和顺式二胺铂（CDDP）的siRNA共同递送至叶酸受体-α（FRA）过度表达的H1299肺癌细胞。使用 FRA 靶向 NP 共同递送 HuR siRNA 和 CDDP 的治疗效果明显优于单独治疗。此外，与非靶向 NP 相比，FRA 靶向 NP 对肺癌细胞表现出更好的细胞毒性。最后，NP 对正常 MRC9 肺成纤维细胞显示出可忽略不计的毒性。因此，本研究证明 FRA 靶向 Den 纳米颗粒系统作为合适的载体，用于在肺癌细胞中靶向共递送 siRNA 和化疗药物。使用叶酸缀合的树枝状聚合物-聚乙烯亚胺 (Den-PEI) 纳米颗粒测试了一种新型化疗 (CDDP)-siRNA (HuR) 组合在肺癌细胞中的抗肿瘤效率。这种 Den-PEI-CDDP-HuR-FA 系统在叶酸受体 α (FRA) 过表达的肺癌细胞中表现出良好的靶向递送特性和增强的细胞摄取。靶向纳米颗粒递送还诱导细胞凋亡，并在肺癌细胞中证明了 CDDP 和 HuR siRNA 的有效联合治疗活性。
Co-administration of functionally distinct anti-cancer agents has emerged as an efficient strategy in lung cancer treatment. However, a specially designed drug delivery system is required to co-encapsulate functionally different agents, such as a combination of siRNA and chemotherapy, for targeted delivery. We developed a folic acid (FA) -conjugated polyamidoamine dendrimer (Den) -based nanoparticle (NP) system for co-delivery of siRNA against HuR mRNA (HuR siRNA) and cis-diamine platinum (CDDP) to folate receptor-α (FRA) -overexpressing H1299 lung cancer cells. The co-delivery of HuR siRNA and CDDP using the FRA-targeted NP had a significantly greater therapeutic effect than did individual therapeutics. Further, the FRA-targeted NP exhibited improved cytotoxicity compared to non-targeted NP against lung cancer cells. Finally, the NP showed negligible toxicity towards normal MRC9 lung fibroblast cells. Thus, the present study demonstrates FRA-targeted Den nanoparticle system as a suitable carrier for targeted co-delivery of siRNA and chemotherapy agents in lung cancer cells. A novel chemotherapeutic (CDDP)-siRNA (HuR) combination was tested for its anti-tumor efficiency in lung cancer cells using folic acid conjugated Dendrimer-Polyethlyeneimine (Den-PEI) nanoparticles. This Den-PEI-CDDP-HuR-FA system showed favorable properties for targeted delivery and enhanced cell uptake in folate receptor alpha (FRA) overexpressing lung cancer cells. The targeted nanoparticle delivery also induced apoptosis, and demonstrated efficient combined therapeutic activity of CDDP and HuR siRNA in lung cancer cells.
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影响因子：
4.9
作者：
Babu, Anish;Wang, Qi;Ramesh, Rajagopal
通讯作者：
Ramesh, Rajagopal
影响因子：
10.2
作者：
Muralidharan R;Babu A;Amreddy N;Basalingappa K;Mehta M;Chen A;Zhao YD;Kompella UB;Munshi A;Ramesh R
通讯作者：
Ramesh R
影响因子：
8
作者：
Narsireddy A;Vijayashree K;Adimoolam MG;Manorama SV;Rao NM
通讯作者：
Rao NM
影响因子：
4
作者：
Haxton, Katherine J.;Burt, Helen M.
通讯作者：
Burt, Helen M.
影响因子：
0.8
作者：
Madaan K;Kumar S;Poonia N;Lather V;Pandita D
通讯作者：
Pandita D