MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
Nanoscale. 2016 May 5;8(18):9572-82. doi: 10.1039/c6nr02181f.
The adverse effects of metal-based nanoparticles on human beings and the environment have received extensive attention recently. It is urgently required to develop a simple and effective method to suppress the toxicity of metal-based nanomaterials. In this study, a hydrophobic antioxidant and a chelation agent curcumin (CUR) were encapsulated into bovine serum albumin (BSA) particles by a simple co-precipitation method, and followed by glutaraldehyde cross-linking. The CUR/BSA particles had an average size of 300 nm in diameter with a negatively charged surface and sustained curcumin release properties. The cellular uptake and cytotoxicity of CUR/BSA particles were followed on A549 cells, HepG2 cells and RAW264.7 cells. The CUR/BSA particles had higher intracellular accumulation and lower cytotoxicity compared with the free curcumin at the same drug concentration. The CUR/BSA particles could suppress the cytotoxicity generated by CuO nanoparticles as a result of decrease of both the intracellular reactive oxygen species (ROS) level and Cu(2+) concentration, while the free curcumin did not show any obvious detoxicating effect. The detoxicating effects of CUR/BSA particles were further studied in an intratracheal instillation model in vivo, demonstrating significant reduction of toxicity and inflammatory response in rat lungs induced by CuO nanoparticles. The concept-proving study demonstrates the potential of the CUR/BSA particles in suppressing cytotoxicity of metal-based nanomaterials, which is a paramount requirement for the safe application of nanotechnology.
最近，人们对基于金属的纳米粒子对人类和环境的不良影响给予了广泛关注。迫切需要开发一种简单有效的方法来抑制金属基纳米材料的毒性。在这项研究中，一种疏水性抗氧化剂和一种螯合剂姜黄素（CUR）通过简单的共沉淀法被包裹到牛血清白蛋白（BSA）颗粒中，然后用戊二醛交联。CUR/BSA 颗粒的平均粒径为 300nm，表面带负电荷，并具有持续释放 CUR 的特性。在 A549 细胞、HepG2 细胞和 RAW264.7 细胞上研究了 CUR/BSA 颗粒的细胞摄取和细胞毒性。与相同药物浓度的游离姜黄素相比，CUR/BSA 颗粒具有更高的细胞内积累和更低的细胞毒性。CUR/BSA 颗粒通过降低细胞内活性氧（ROS）水平和 Cu（2+）浓度，能够抑制 CuO 纳米粒子产生的细胞毒性，而游离姜黄素则没有表现出明显的解毒作用。在体内气管滴注模型中进一步研究了 CUR/BSA 颗粒的解毒作用，证明其能够显著降低 CuO 纳米粒子诱导的大鼠肺部毒性和炎症反应。这项概念验证研究表明，CUR/BSA 颗粒在抑制金属基纳米材料的细胞毒性方面具有潜力，这是纳米技术安全应用的首要要求。
