ROS-responsive biomimetic nanoparticles for potential application in targeted anti-atherosclerosis

Abstract

The development of nanomedicines provides new opportunities for the treatment of atherosclerosis (AS) due to their great advantages such as the improved drug solubility, enhanced bioavailability and reduced side effects. Despite these advantages, nanomedicines are still facing some challenges. The problems remain in the short circulation life, lack of specific targeting and poor drug release controllability. In order to overcome the shortages of conventional nanomedicines, the combination of biomimetic strategy with smart nanoagents has been proposed. In light with the high reactive oxygen species (ROS) level in AS microenvironment and the fact that macrophages play a critical role in the pathogenesis of AS, we fabricated ROS-responsive biomimetic nanoparticles (NPs), which camouflaged macrophage membrane (MM) on ROS-responsive NPs loaded with rapamycin (RNPs) for potential application in AS therapy. The resulting ROS-responsive biomimetic NPs (MM/RNPs) exhibited favorable hydrodynamic size with negative surface charge, retained the functional proteins from MM, and showed ROS-responsive drug release. Because of the biomimetic camouflaging on surface, MM/RNPs could effectively escape from macrophages uptake and target to inflammatory endothelial cells. Meanwhile, MM/RNPs could inhibit the proliferation of macrophages and smooth muscle cells in vitro. Furthermore, the MM-coated NPs were found to be nontoxic in both cytotoxicity assay and in vivo toxicity evaluation. Consequently, these results demonstrated that MM/RNPs could be a potential candidate of drug delivery system for safe and effective anti-AS applications.

COVID-19 inflammation and implications in drug delivery

“…The oxidative stress, mainly resulting from the infiltration of neutrophils releasing reactive oxygen species (ROS), is another biochemical stimulus that can be used to trigger the release of therapeutics in inflammation sites during lung injuries [ 103 , 104 ]. In addition to the selective drug release, ROS materials may scavenge oxygens species contributing to inflammation.…”

Inflammation, Oxidative Stress, Senescence in Atherosclerosis: Thioredoxine-1 as an Emerging Therapeutic Target

“…A new biomimetic drug delivery system consisting of nanoparticles that are coated with macrophage membrane and responsive to ROS enables targeted pharmacotherapy for atherosclerosis in mice while also suppressing local inflammation by sequestering inflammatory factors [ 231 ]. Hence, macrophage-biomimetic delivery system can achieve inflammation tropism without the need for specific targeting molecules; this strategy might hold promise for other inflammatory diseases [ 232 ].…”

Recent Advances in ROS-Sensitive Nano-Formulations for Atherosclerosis Applications

“…Recently, cell-derived biomimetic nanoparticles have attracted extensive attention due to their long-term blood circulation, lower immunogenicity, and enhanced target capability compared to traditional nanoparticles [ 98 ]. In recent studies, biomimetic delivery systems derived from macrophage membranes were developed to encapsulate ROS-responsive nanoparticles for atherosclerosis treatment [ 38 , 99 , 100 ]. These cellular function-driven approaches can achieve targeted delivery to inflammatory tissues without resorting to additional target molecules, as well as reduce the clearance of nanoparticles by the reticuloendothelial system.…”

“…This biomimetic strategy could facilitate nanoparticle escape from macrophage clearance, thereby prolonging blood circulation time. Moreover, this biomimetic nano-formulation had a favorable biocompatibility and significantly inhibited the proliferation of macrophages in an in vitro study, showing potential application prospect for atherosclerosis treatment [ 38 ].…”

“…In particular, stimulus-sensitive nano-formulations are capable of accelerating cargo release under specific trigger conditions, such as ROS, pH, temperature, and enzymes [ 29 , 30 , 31 ]. Responding to the pathological ROS differences, desirable multifunctional carriers are able to reveal great changes in solubility and/or cleavable bonds in the molecular structures for “on-demand” cargo release at the atherosclerosis lesion [ 13 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Thus, pharmacological targeting of ROS-sensitive nano-formulations represents a promising therapeutic avenue for safe and effective atherosclerosis management.…”