Advancements in dual-targeting nanoparticle strategies for enhanced atherosclerosis therapy: Overcoming limitations of single-targeting approaches

Atherosclerosis treatment remains challenging, particularly in terms of developing effective targeted drug delivery strategies to enhance therapeutic efficacy. As research advances, considerable attention has been paid to identifying specific cell types and subcellular organelles-based on molecular mechanisms, damage progression, and drug action-to design next-generation nanoformulations with greater precision. Dual-targeting nanoparticles, which integrate numerous targeting modalities, offer a promising approach to precise drug delivery to pathological plaque sites. By enabling sequential and synchronous navigation of the targeting moieties, these strategies offer greater control over drug delivery than conventional methods. In this review, we discuss the pathological process of atherosclerosis and examine the progress made in its treatment using rationally designed nanoparticles over recent decades. We critically evaluate the limitations of single-targeting strategies and explore potential areas for improvement. Further, we provide a comprehensive overview of the classification and core principles of dual-targeting methods, thereby evaluating their efficiency. Finally, we discuss the design and application of strategies that integrate targeting ligands with stimulus-responsive moieties or nanobiomimetic techniques, thereby demonstrating their potential to address ligand-based dual-targeting nanotechnology limitations.