Reynolds Lacy, Mulik Rohit S, Wen Xiaodong, Dilip Archana, Corbin Ian R
Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Nanomedicine (Lond). 2014 Jul;9(14):2123-41. doi: 10.2217/nnm.13.187. Epub 2014 Jan 7.
The natural omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has recently been credited for possessing anticancer properties. Herein, we investigate the cytotoxic actions of DHA-loaded low-density lipoprotein (LDL) nanoparticles in normal and liver cancer cells.
MATERIALS & METHODS: LDL-DHA nanoparticles were prepared and subjected to extensive biophysical characterization. The therapeutic utility of LDL-DHA nanoparticles was evaluated in normal and malignant murine hepatocyte cell lines, TIB-73 and TIB-75, respectively.
RESULTS & DISCUSSION: The engineered LDL-DHA nanoparticles possessed enhanced physical and oxidative stabilities over native LDL and free DHA. Dose-response studies showed that therapeutic doses of LDL-DHA nanoparticles that completely killed TIB-75 were innocuous to TIB-73. The selective induction of lipid peroxidation and reactive oxygen species in the cancer cells was shown to play a central role in LDL-DHA nanoparticle-mediated cytotoxicity.
In summary, these findings indicate that LDL-DHA nanoparticles show great promise as a selective anticancer agent against hepatocellular carcinoma.
天然ω-3多不饱和脂肪酸二十二碳六烯酸（DHA）最近被认为具有抗癌特性。在此，我们研究了负载DHA的低密度脂蛋白（LDL）纳米颗粒在正常细胞和肝癌细胞中的细胞毒性作用。
制备了LDL-DHA纳米颗粒并进行了广泛的生物物理表征。分别在正常和恶性小鼠肝细胞系TIB-73和TIB-75中评估了LDL-DHA纳米颗粒的治疗效用。
工程化的LDL-DHA纳米颗粒比天然LDL和游离DHA具有更高的物理稳定性和氧化稳定性。剂量反应研究表明，能完全杀死TIB-75的治疗剂量的LDL-DHA纳米颗粒对TIB-73无害。癌细胞中脂质过氧化和活性氧的选择性诱导在LDL-DHA纳米颗粒介导的细胞毒性中起核心作用。
总之，这些发现表明LDL-DHA纳米颗粒作为一种针对肝细胞癌的选择性抗癌剂具有巨大潜力。
