活性氧刺激响应纳米载体

纳米载体一般是由天然高分子或人工合成高分子组成的、纳米级范畴的运输系统,具有减少药物毒性、提高药物的靶向性、增加药物有效性等优点。随着生物医学技术的进步,有研究表明,作为氧化代谢产物的活性氧(ROS)在疾病部位常常伴随着过表达的异常现象。基于此,近年来ROS刺激响应纳米载体获得了关注和发展,以不同响应机制的ROS响应基团为基础,发展了一系列的ROS响应纳米载体,实现了疾病部位ROS刺激下的药物特异性可控释放。该文聚焦于近年来常用于纳米载体的ROS响应基团,依据元素划分为两大类:硫族元素类响应基团(硫醚、缩硫酮、硒化物、二硒化物、碲化物)和其他元素类响应基团(芳香硼酸酯、过氧草酸酯、二茂铁);通过不同的设计理念将其引入纳米载体,根据ROS响应纳米载体的不同响应机制(疏水-亲水相变、断裂),探讨了载体各自的ROS响应情况、体外药物释放情况,以及在活体中的应用情况。

Reactive oxygen species stimuli-responsive nanocarriers

Nanocarriers are nanoscale delivery systems composed of natural or synthetic polymers, which are advantageous in reducing drug toxicity while improving drug targeting and utilization. With the advancement of biomedical technology, it is revealed that reactive oxygen species (ROS), a class of oxidative metabolites, show abnormal overexpression in disease-related parts of the body. Hence, ROS stimuli-responsive nanocarriers have gained increasing attention, and recent developments are expected to realize controllable drug release. Based on linkers with different ROS-responsive mechanisms, a series of ROS-responsive nanocarriers have been designed to achieve specific controlled drug release under the stimulation of the ROS at the disease site. This article mainly focuses on ROS-responsive linkers, which have been commonly used for the synthesis of nanocarriers in recent years. Accordingly, the linkers are classified as chalcogen-containing responsive linkers (thioether, thioketal, selenide, diselenide, and telluride) and responsive linkers containing other elements (arylboronic ester, ferrocene, and peroxalate ester). ROS stimuli-responsive nanocarriers are fabricated by introducing ROS-responsive linkers in different design principles. Owing to the ROS-responsive linkers, the nanocarriers follow different responsive mechanisms, including hydrophobic-to-hydrophilic phase transition and cleavage. This article discusses the degree of responsiveness of nanocarri-ers and the specific release of drugs from nanocarriers upon ROS-stimuli, as well as their applications in vivo. In particular, on the basis of intelligent drug release and precision medicine, this article also emphasizes the importance of the biocompatibility and biodegradability of nanocarriers.