Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada.
J Control Release. 2015 Jul 10;209:110-9. doi: 10.1016/j.jconrel.2015.04.025. Epub 2015 Apr 22.
Curcumin is a phytochemical with diverse molecular targets and is well known for its anti-tumor potential. However, it has limited application in cancer therapy because curcumin undergoes rapid oxidative degradation at physiological conditions resulting in poor stability and bio-availability. In this study, we were able to suppress curcumin's oxidative degradation by encapsulating it in a nanoparticle that also acts as a radical scavenger. We prepared curcumin-loaded pH-sensitive redox nanoparticles (RNP(N)) by self-assembling amphiphilic block copolymers conjugated with reactive oxygen species (ROS) scavenging nitroxide radicals to ensure the delivery of minimally degraded curcumin to target regions. In vitro analysis confirmed that the entrapment of both curcumin and nitroxide radicals in the hydrophobic core of RNP(N) suppressed curcumin degradation in conditions mimicking the physiological environment. Evaluation of apoptosis-related molecules in the cells, such as ceramides, caspases, apoptosis-inducing factor, and acid ceramidase revealed that curcumin loaded RNP(N) induced strong apoptosis compared to free curcumin. Lastly, intravenous injection of curcumin loaded RNP(N) suppressed tumor growth in vivo, which is due to the increased bio-availability and significant ROS scavenging at tumor sites. These results demonstrated that RNP(N) is a promising drug carrier with unique ROS-scavenging abilities, and it is able to overcome the crucial hurdle of curcumin's limitations to enhance its therapeutic potential.
姜黄素是一种具有多种分子靶点的植物化学物质，以其抗肿瘤潜力而闻名。然而，由于其在生理条件下会迅速发生氧化降解，导致稳定性和生物利用度差，因此在癌症治疗中的应用有限。在这项研究中，我们通过将其包裹在纳米颗粒中，同时也作为自由基清除剂，从而抑制了姜黄素的氧化降解。我们通过自组装与活性氧（ROS）清除氮氧自由基偶联的两亲嵌段共聚物，制备了负载姜黄素的 pH 敏感氧化还原纳米颗粒（RNP（N）），以确保将最小降解的姜黄素递送到靶区。体外分析证实，姜黄素和氮氧自由基都被包封在 RNP（N）的疏水核中，抑制了模拟生理环境的条件下姜黄素的降解。对细胞中与细胞凋亡相关的分子（如神经酰胺、半胱天冬酶、凋亡诱导因子和酸性神经酰胺酶）的评估表明，与游离姜黄素相比，负载姜黄素的 RNP（N）诱导了强烈的细胞凋亡。最后，静脉注射负载姜黄素的 RNP（N）在体内抑制了肿瘤生长，这是由于在肿瘤部位增加了生物利用度和显著的 ROS 清除作用。这些结果表明，RNP（N）是一种具有独特 ROS 清除能力的有前途的药物载体，它能够克服姜黄素的关键限制，增强其治疗潜力。
