Stimulus-responsive nanoparticles for therapeutic stabilization of atherosclerosis

Atherosclerosis is a critical cardiovascular complication in which progressive accumulation of fats, cholesterol, and several other cellular debris in the artery wall (to form the plaque), and obstructs blood flow. The lipid-lowering, anti-inflammatory, and blood-thinning agents are mostly the first line of treatment clinically; however, the successful delivery of these agents at the plaque site is a long-standing challenge. While the application of drug delivery nanoparticles, up to a greater extent, helps overcome these challenges associated with free drug delivery, off-target toxicity due to uncontrolled release of encapsulated drug from such nanoparticles limits their use in atherosclerosis treatment. There is an enormous interest in developing stimuli-responsive nanoparticles (SRNs) system that allows adjusting the rate of drug release either due to endogenous trigger like acidic pH, elevated enzyme level, and increased oxidative stress present at plaque site or due to externally applied stimulus (exogenous trigger) like light, magnet, and ultrasound. In both cases, the use of SRNs enhances the therapeutic outcome and minimizes apparent toxicity due to the non-selective accumulation of drug-loaded nanoparticles. Both the endogenous and exogenous strategies were found promising in treating atherosclerosis more precisely and safely. In this chapter, we have described different types of SRNs (both endogenous and exogenous) developed for treating atherosclerosis by highlighting their design approach, working mechanisms, suitability, and limitations in the context of atherosclerosis treatment. Lastly, we also discussed key technical challenges in designing such SRNs for atherosclerosis and shared future directions, potentially overcoming these challenges.