作者
Meghna Talekar, Malav Trivedi, Parin Shah, Qijun Ouyang, Adwait Oka, Srujan Gandham, Mansoor M Amiji
发表日期
2016/4/1
期刊
Molecular Therapy
卷号
24
期号
4
页码范围
759-769
出版商
Elsevier
简介
Mutations in KRAS and p53 signaling pathways contribute to loss of responsiveness to current therapies and a decreased survival in lung cancer. In this study, we have investigated the delivery and transfection of wild-type (wt-) p53 and microRNA-125b (miR-125b) expressing plasmid DNA, in SK-LU-1 human lung adenocarcinoma cells as well as in KrasG12D/p53fl/fl (KP) genetically engineered mouse model of lung cancer. Systemic plasmid DNA delivery with dual CD44/EGFR-targeted hyaluronic acid (HA)-based nanoparticles (NPs) resulted in a 2- to 20-fold increase in wt-p53 and miR-125b gene expression in SK-LU-1 cells. This resulted in enhanced apoptotic activity as seen with increased APAF-1 and caspase-3 gene expression. Similarly, in vivo evaluations in KP mouse model indicated successful CD44/EGFR-targeted delivery. Tumor growth inhibition and apoptotic induction were also observed with (wt …
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M Talekar, M Trivedi, P Shah, Q Ouyang, A Oka… - Molecular Therapy, 2016