Abstract:

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.

Key words: reactive oxygen species (ROS), stimuli-responsive, nanocarriers, nanoparticles (NPs)