Programming the beating heart with polymer catalysis: a therapeutic microenvironment revolution

Cardiovascular diseases (CVDs) represent a paramount global health burden, with their pathogenesis rooted in a dynamically dysregulated tissue microenvironment characterized by sustained oxidative stress, compromised nitric oxide bioavailability, hyperactive thrombogenesis, and calcium homeostasis disruption. This review moves beyond the conventional view of polymers as inert drug carriers. Instead, it articulates a shift toward regarding them as intelligent, stimuli-responsive catalytic platforms. These platforms can actively sense and remodel the pathological microenvironment. We meticulously detail the design principles underpinning these systems, encompassing enzyme-mimetic copolymer networks that replicate natural catalytic cycles, self-assembled gas therapy nanoparticles with geometrically confined active sites, intelligent hydrogels enabling on-demand therapeutic release, and surface-functionalized vectors for precise endothelial targeting. A key differentiator is the inherent advantage of polymeric architectures. By leveraging dynamic covalent bonding, tunable topology, and biocompatible backbones, these systems achieve superior biosafety and more seamless integration with biological processes than conventional metal-based nanocatalysts. The review critically evaluates their transformative therapeutic performance across a spectrum of CVDs, including acute myocardial infarction, atherosclerotic plaque stabilization, and ischemia-reperfusion injury, thereby establishing a transformative design philosophy for catalytic cardiovascular medicine. Finally, we delineate the prevailing translational hurdles, such as long-term biosafety and scalable manufacturing, and outline future directions, positing that polymer nanocatalysis is poised to become a cornerstone of next-generation, personalized theranostic strategies against CVDs.