# Advancing the Landscape of RNAi Nanotherapeutics for Ischemic Heart Disease

## TL;DR

This paper reviews how RNAi nanomedicine is transforming treatment for heart diseases by enabling precise gene regulation.

## Contribution

The paper provides a comprehensive overview of RNAi nanotherapeutics for ischemic heart disease and outlines design principles for effective delivery systems.

## Key findings

- RNAi nanomedicine enables tailored gene regulation for cardiac repair.
- Key design principles for efficient delivery of RNAi therapeutics are identified.
- Translational challenges and opportunities for RNAi in cardiovascular therapy are discussed.

## Abstract

Ischemic heart disease (IHD) remains the foremost cause of mortality worldwide, characterized by extensive myocardial injury following infarction with limited regenerative capacity of the adult mammalian heart. RNA interference (RNAi) nanotechnology is revolutionizing cardiac therapy by leveraging the sequence‐oriented gene regulation that can overcome the obstacles hindering conventional therapeutic approaches. Here, we outline the evolving landscape of RNAi nanomedicine for cardiac repair, with an emphasis on therapeutic advances in myocardial infarction and atherosclerosis. We further discuss design considerations for constructing effective nanosystems, underscoring the critical principles by bridging mechanistic insights with material engineering. Finally, we delineate the translational pathway from bench to bedside, detailing current challenges and highlighting prospective opportunities for advancing RNAi therapeutics in cardiovascular therapy.

RNA interference (RNAi) nanomedicine revolutionizes treatment regimens for ischemic heart diseases by enabling tailored, sequence‐anchored gene regulation. This review highlights the recent advances in nanotechnology‐driven RNAi therapeutics for myocardial ischemia and discusses the key design principles that govern efficient delivery, providing critical insights into the rational design of next‐generation nanoplatforms for cardiac repair.