Engineered Therapeutic Nanoplatforms for Ischemic Heart Disease Treatment Vis Cardiac Microenvironment Reprogramming

Ischemic heart disease (IHD), the leading cause of death worldwide, progresses through acute, transitional, and end-stage phases, forming a "oxidative stress-inflammation-fibrosis" vicious cycle. Current therapies face major limitations: reperfusion, crucial in the acute phase, fails to prevent secondary injury, while conventional pharmacotherapy is hindered by low bioavailability, off-target effects, systemic toxicity, and limited therapeutic efficacy. Although nanotechnology shows immense potential for targeted delivery and precise regulation of IHD pathology, a critical gap remains in existing reviews-namely, the lack of systematic analysis on how nanomaterials target stage-specific pathologies defined by distinct core mechanisms (acute oxidative stress, transitional inflammation, end-stage fibrosis) to achieve full-course intervention. This review addresses this gap by systematically outlining the core pathology and treatment bottlenecks of each IHD stage, critically evaluating recent advances in nanomaterial applications for stage-specific targeting and full-course intervention. Through in-depth analysis of current nanotherapy challenges and limitations, it proposes future research directions, providing a theoretical basis and design concepts for developing innovative nanotechnology-based IHD therapies and mechanistic research.