Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur (UniKL RCMP), 30450 Perak, Malaysia.
ASASIpintar UKM Program, Pusat Genius@Pintar Negara, Universiti Kebangsaan Malaysia, 43600, Bangi, Selangor, Malaysia; Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), 50300, Kuala Lumpur, Malaysia.
Food Chem Toxicol. 2022 May;163:112976. doi: 10.1016/j.fct.2022.112976. Epub 2022 Mar 29.
Curcumin has been used for chronic lung diseases management due to its diversified molecular actions. However, the potential cytotoxicity which occurs in cells following the exposure to high concentrations of curcumin has been overlooked. This study evaluated the toxic events of curcumin nanoparticles (Cur-NPs) with alterable surface polarity in alveolar macrophages (NR8383). We aimed to establish the correlation between the toxicity of Cur-NPs with different surface charges and the internalization mechanisms of the NPs. Toxicity data showed that positively charged Cur-NPs (IC: 9.77 ± 0.5 μg/mL) was the most potent against NR8383, followed by negatively charged Cur-NPs (IC:13.33 ± 0.9 μg/mL) and neutral Cur-NPs (IC:18.68 ± 1.2 μg/mL). Results from mitochondrial membrane potential, ATP content and intracellular ROS in NR8383 showed similar ranking to the toxicity assay. The predominant uptake pathway for positively and negatively charged Cur-NPs was via clathrin-mediated endocytosis, while neutral Cur-NPs was internalized via phagocytosis, micropinocytosis and clathrin-mediated endocytosis. Positively charged Cur-NPs mediates the cytotoxicity of NR8383 via lysosomal and mitochondrial-associated destabilization upon entry. In conclusion, the cytotoxicity of Cur-NPs on NR8383 is surface-charge dependent, which in turn is associated to the uptake pathway and localization of Cur-NPs in cells.
姜黄素因其多样化的分子作用而被用于慢性肺部疾病的治疗。然而，人们忽视了细胞在暴露于高浓度姜黄素后发生的潜在细胞毒性。本研究评估了具有可变化学性质的姜黄素纳米粒子（Cur-NPs）对肺泡巨噬细胞（NR8383）的毒性作用。我们旨在建立 Cur-NPs 不同表面电荷的毒性与 NPs 内化机制之间的相关性。毒性数据表明，带正电荷的 Cur-NPs（IC：9.77±0.5μg/mL）对 NR8383 的抑制作用最强，其次是带负电荷的 Cur-NPs（IC：13.33±0.9μg/mL）和中性 Cur-NPs（IC：18.68±1.2μg/mL）。NR8383 中的线粒体膜电位、ATP 含量和细胞内 ROS 的结果与毒性测定相似。带正电荷和负电荷的 Cur-NPs 的主要摄取途径是网格蛋白介导的内吞作用，而中性 Cur-NPs 则通过吞噬作用、微饮作用和网格蛋白介导的内吞作用被内化。带正电荷的 Cur-NPs 通过进入细胞后溶酶体和线粒体相关的不稳定来介导 NR8383 的细胞毒性。总之，Cur-NPs 对 NR8383 的细胞毒性依赖于表面电荷，而这又与 Cur-NPs 在细胞中的摄取途径和定位有关。
