Ganeshkumar Moorthy, Ponrasu Thangavel, Raja Modhugoor Devendiran, Subamekala Muthaiya Kannappan, Suguna Lonchin
Department of Biochemistry, CSIR-Central Leather Research Institute, Council of Scientific and Industrial Research, Adyar, Chennai 600020, India.
Bio-Products Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai 600020, India.
Spectrochim Acta A Mol Biomol Spectrosc. 2014 Sep 15;130:64-71. doi: 10.1016/j.saa.2014.03.097. Epub 2014 Apr 5.
The aim of this study was to synthesize green chemistry based gold nanoparticles using liver specific biopolymer and to develop a liver cancer targeted drug delivery system with enhanced efficacy and minimal side effects. Pullulan stabilized gold nanoparticles (PAuNPs) were coupled with 5-Fluorouracil (5-Fu) and folic acid (Fa) which could be used as a tool for targeted drug delivery and imaging of cancer. The toxicity of 5-Fu, 5-Fu adsorbed gold nanoparticles (5-Fu@AuNPs), Fa-coupled 5-Fu adsorbed gold nanoparticles (5-Fu@AuNPs-Fa), was studied using zebrafish embryo as an in vivo model. The in vitro cytotoxicity of free 5-Fu, 5-Fu@AuNPs, 5-Fu@AuNPs-Fa against HepG2 cells was studied and found that the amount of 5-Fu required to achieve 50% of growth of inhibition (Ic50) was much lower in 5-Fu@AuNP-Fa than in free 5-Fu, 5-Fu@AuNPs. The in vivo biodistribution of PAuNPs showed that higher amount of gold had been accumulated in liver (54.42±5.96 μg) than in other organs.
本研究的目的是使用肝脏特异性生物聚合物合成基于绿色化学的金纳米颗粒，并开发一种具有更高疗效和最小副作用的肝癌靶向给药系统。支链淀粉稳定的金纳米颗粒（PAuNPs）与5-氟尿嘧啶（5-Fu）和叶酸（Fa）偶联，可作为癌症靶向给药和成像的工具。以斑马鱼胚胎为体内模型，研究了5-Fu、5-Fu吸附的金纳米颗粒（5-Fu@AuNPs）、Fa偶联的5-Fu吸附的金纳米颗粒（5-Fu@AuNPs-Fa）的毒性。研究了游离5-Fu、5-Fu@AuNPs、5-Fu@AuNPs-Fa对HepG2细胞的体外细胞毒性，发现5-Fu@AuNP-Fa中实现50%生长抑制（Ic50）所需的5-Fu量远低于游离5-Fu、5-Fu@AuNPs。PAuNPs的体内生物分布表明，肝脏中积累的金量（54.42±5.96μg）高于其他器官。
